A 74-year-old man presented with sudden headache. A left VA dissecting aneurysm (15 × 6 mm) coexisting with a right internal carotid artery-posterior communicating artery aneurysm was found by MRI at a neighborhood clinic. He had a medical history of hypertension and heavy smoking (30 cigarettes per day for 40 years). On preoperative MRI, the dilated segment started at the height of the jugular foramen, ran transversely at the height of the 7–8th nerves toward the contralateral side, and ended at the point exceeding the midline (). The distal end was >20 mm proximal to the VA union. On preoperative DSA, the common trunk of the anterior inferior cerebellar artery (AICA)-PICA originated from the basilar artery, while the affected V4 had no angiographically identifiable branches (). The contralateral VA was as developed as the affected side. In addition to the irregular-shaped VA aneurysm in the subacute phase, there were other unruptured aneurysms. The patient also requested treatment to allow early return to his work (taxi driver). Thus, we decided to treat the left VA aneurysm at 2 months after onset.
It was impossible to maintain the left VA by reconstructive clipping because of the aneurysm shape. However, it was possible to secure the distal neck and trap the aneurysm because it was located caudal to the 7–8th nerves. PICA revascularization was not necessary because the common trunk of the AICA-PICA was well-developed. Note that there was >20 mm space between the distal neck to the VA union. Furthermore, there was a concern that many brainstem perforators would be occluded because of thromboembolism after blinding of this segment by trapping. Thus, to preserve the anterograde blood flow of the VA, it was reconstructed using RAG to anastomose the V4 segment just distal to the aneurysm and the extracranial V3 segment (V3-RAG-V4 bypass) (, ). The actual surgical procedures of case 2 is shown in .


A 59-year-old man felt sudden headache and dizziness twice in a year. He visited a neighborhood clinic and a right VAFA (10 × 6 mm) was detected. Conservative therapy was selected. However, a third attack occurred with dysarthria and gait disturbance and he visited the emergency department of our hospital near his workplace. He had a medical history of hypertension and hyperlipidemia, and a heavy smoking history (30 cigarettes per day for 30 years).
MRI after admission revealed expansion of the right VAFA (19 × 16 mm) that compressed the lower pons from the anterior side, while the intraluminal thrombus was increased compared with preadmission MRI (). Preoperative DSA showed that the dilated segment of the right VA started 12-mm proximal, and ended just proximal, to the VA union. The right side had a common trunk of the AICA-PICA, while the PICA was absent. However, there was a relatively thick branch (0.8 mm in diameter) feeding the lower vermis, lower pons, and medulla oblongata that arose from the V4 segment just distal to the penetrating part of the posterior dura (, blue arrowhead). In addition, no angiographically identifiable branch was found. The contralateral VA was well-developed.
No other cause was found to explain his symptoms. Thus, brainstem compression caused by expansion of the thrombotic part of the aneurysm was considered the main cause. For treatment, the distal end of the aneurysm was positioned high and contralaterally displaced, making it difficult to perform reconstructive clipping as for case 1 or VA reconstruction as for case 2. Thus, we selected proximal ligation. The strategy was to reduce blood flow into the dilated segment of the aneurysm while maintaining the VA perforators by allowing the retrograde blood flow via the VA union to pass through the aneurysm and outflow to the VA perforator (). In this situation, we had no choice but to make the distal segment of the ligation clip the so-called “perforator end,” which is hemodynamically prone to obstruction. Nevertheless, the potential for perforator obstruction was considered to be relatively low compared with aneurysmal trapping.
Intraoperatively, a perforator arose from the V4 segment just proximal to the aneurysm and there was no distance for clip application between the proximal neck to this perforator (, , black arrowhead). Thus, the proximal portion of this perforator was ligated while ensuring visually that there was no other conspicuous VA perforator. The anterograde blood flow of the VA was allowed to flow out to the aforementioned relatively thick branch from the V4 (, , blue arrowhead). Additionally, a flow-augmentation to the right PICA through the V3-RAG-PICA bypass secured the perfusion of the right AICA-PICA region to reduce the hemodynamic load on the contralateral VA. This was expected to be a detour to substitute for the VA trunk (, blue arrow) in case the contralateral VA become occluded in the future. The actual surgical procedures of case 3 is shown in .


A 67-year-old male presented to the emergency department with two weeks of malaise, chills, and shortness of breath. He also complained of a one-day history of asymmetric polyarthritis, which made it difficult for him to walk. He reported that the pain was worse in the left wrist and left knee. He had experienced a previous episode of similar pain that had resolved with long-term treatment with indomethacin and prednisone. He also had associated left knee swelling. He had been having complaints of flu-like syndrome for the last two weeks. He denied having any difficulties such as nausea, vomiting, constipation, diarrhea, rash, temporal tenderness, redness of eyes, dysuria, genital discharge, blurry visions, and neck stiffness. He also denied any falls. He also had a prior history of smoking.
On admission, he had a new oxygen requirement of 2L. The temperature was 36.3 °C, blood pressure was 125/68 mmHg, pulse was 89 bpm, respiratory rate was 20/minute, and oxygen saturation was 90% on 2L. On physical exam, he was found to have bilateral tenderness in his knees, wrist, elbows, hips, and shoulders. His lab workup revealed a white blood cell count of 9.3 x 10E3/μL, hemoglobin of 15 g/dL, hematocrit of 46%, and platelet count of 235 x 10E3/μL.
The X-ray of the left wrist showed no osseous abnormality, but the X-ray of the left knee showed a large joint effusion with a radiopaque foreign body in the suprapatellar region (Figure ).
Orthopedic surgery was consulted to aspirate his left knee. Aspirate revealed uric acid crystals, calcium pyrophosphate crystals, 53,000 nucleated cells with 87% neutrophils, and an unremarkable gram stain. Additionally, a chest X-ray was ordered to evaluate the shortness of breath, which revealed right upper lobe pneumonia (Figure ).
This was followed by a respiratory panel, which was positive for C. pneumoniae and rhinovirus. He was diagnosed with inflammatory arthritis secondary to gout and pseudogout as well as ReA secondary to C. pneumoniae.
He was started on an indomethacin course for one week with significant improvement in his arthralgias. For his C. pneumoniae, ceftriaxone and doxycycline were initially commenced followed by a de-escalation to doxycycline. He was discharged on azithromycin for a total five-day treatment course.


A 65-year-old man with synchronous prostate and rectal cancers was referred to us in August 2017. His baseline health was excellent. He experienced hematochezia, decreased stool caliber, and sensation of incomplete stool emptying at presentation. Laboratory findings included a carcinoembryonic antigen (CEA) level of 6.8 ng/mL. He underwent a colonoscopy that revealed a fungating, nonobstructive mass in the high rectum. Biopsy demonstrated an invasive moderately differentiated adenocarcinoma. Computed tomography abdomen/pelvis showed no evidence of metastases. Magnetic resonance imaging (MRI) demonstrated a clinical T2, N2b, stage IIIB, 2.8-cm rectal tumor (AJCC 8th edition []), along with a suspicious 1.6-cm lesion in the posteromedial aspect of the peripheral zone at the mid prostate that was clinically palpable. His total prostate-specific antigen (PSA) level was 14.1 ng/mL. A subsequent prostate biopsy confirmed adenocarcinoma, which was staged as Gleason 4+3, cT2a, N0, M0, intermediate-risk ().
Before treatment, his American Urological Association (AUA) symptom score was 0 of 35 at baseline. He was able to have erections but had not been sexually active. After a multidisciplinary discussion, the patient commenced PBT targeting both the rectum and the prostate, along with RT to pelvic nodes. For his rectal cancer, he received preoperative chemoradiation therapy with 50 GyE in 25 fractions (including the entire prostatic volume) and concurrent capecitabine. He received a boost of 78 GyE in 39 fractions to the prostate via a sequential boost plan (). The initial rectal plus prostatic plan was given by 2 posterior beams (T270G150 and T270G185 beam angles), and the prostatic boost plan was given by opposed lateral beams. The patient was simulated in the supine position with standard pelvic immobilization and a full bladder. A rectal balloon was not used. Robust optimization was used and planned to the clinical target volume. Ultrasound-guided prostate marker seeds were used for daily image guidance. Dosimetric constraints used for the bladder (V80Gy ≤ 10%, V75Gy ≤ 15%, V65Gy ≤ 40%), rectum (D2cc < 81Gy, V70Gy ≤ 15%, V60Gy ≤ 30%), and small bowel (max point dose < 52 Gy, V50Gy < 2 cm3, V45Gy < 150 cm3) were met with the intensity-modulated proton therapy plan. A comparison plan is provided in . He completed the prescribed course of RT, concurrent chemotherapy, and 6 months of concurrent leuprolide therapy with no grade 3 or greater toxicities. In January 2018, MRI of the pelvis demonstrated significant decrease in size of the rectal mass. His total PSA level was 0.22 ng/mL. In February 2018, the patient underwent a robotic-assisted low anterior resection (LAR) with diverting loop ileostomy and bilateral ureteral stent placement. Final rectal pathology revealed a complete pathologic response including negative lymph nodes. The patient then completed 6 cycles of adjuvant XELOX chemotherapy. In August 2018, his AUA score remained at 0, and he reported no pain, urinary incontinence, dysuria, or hematuria. He had lost his erectile function.
The patient completed ileostomy closure in February 2019, and his PSA level was 0.32 ng/mL at that time. Colonoscopy findings in May 2019 were normal. He reported no dysuria or hematuria. He reported regular bowel movements and formed stools, with slightly increased bowel urgency and frequency since ileostomy closure. In February 2020, he reported occasional minimal urinary leakage. His AUA score remained stable at 15 points. At his latest follow-up, in December 2020 (37 months since end of PBT), he reported only grade 1 chronic side effects. Regarding GI symptoms, he reported tenesmus leading to 2 to 5 bowel movements per day with formed stool. He reported no fecal incontinence or hematochezia. For genitourinary symptoms, his total AUA score was 10 (moderate), and he reported increased urgency, frequency, and difficulty emptying the bladder. He reported no hematuria or urinary incontinence. He continued to have no erectile function. His Eastern Cooperative Oncology Group (0000) score was 0. His PSA level was 0.35 ng/mL, and his CEA level was 2.5 ng/mL. Surveillance imaging showed no evidence of new metastatic disease from either cancer.


A 51-year-old woman was admitted to our endocrinology ward with a history of weakness, anemia, bone pain (since 2 years ago), xanthelasma palpebrarum (Figure ), ulcerative skin lesions (since 5 years ago), and progressive generalized edema (since 1 month ago). She had DI since 12 years ago that was treated with desmopressin. She also received levothyroxine for hypothyroidism. The patient was aware and awake with normal vital signs. Thyroid examination was remarkable for a right lobe nodule, deep tendon reflexes of lower limbs were absent, and the left lower limb had a decreased muscular force (3/5).
Laboratory findings revealed anemia (Hb = 9.1 g/dl), elevated serum alkaline phosphatase (155 U/L), and lactate dehydrogenase (174 U/L), high 24-h urine protein (594 mg), and low serum albumin (2.2 g/dl), and total protein (3.8 g/dl). Serum creatinine, electrolytes, and serum lipid profile were in the normal range except for serum triglycerides of 260 mg/dl. Moreover, anterior pituitary hormones were within the normal range except for a prolactin level of 1447 Miu/ml.
Since hypoalbuminemia and proteinuria were lower than the nephrotic range, upper and lower endoscopies were performed to rule out protein-losing enteropathy, which were normal. Unfortunately, the patient did not agree to push enteroscopy.
A thyroid ultrasound showed a 3*3.2 mm non-calcified nodule in the left lobe and a 48*50*73 mm heterogeneous solid mass with calcified foci in the right lobe. Pathological examination of the right lobe mass fine-needle aspiration reported a benign follicular lesion and BRAF-V600E mutation was negative in the Immunohistochemistry study.
Humeral and femoral plain X-ray showed bilateral symmetric metaphyseal-diaphyseal sclerosis. (Figure ).
A chest CT scan revealed a mild pericardial effusion, bilateral pleural effusion, few mediastinal lymph nodes (SAD = 10 mm), a thyroid nodule (35 × 37 mm with calcification), and small sclerotic lesions in bilateral humerus meta-diaphysis. In echocardiography, mild pericardial effusion and normal LV systolic function were reported.
An MRI examination of the brain showed an empty sella and flattening of the pituitary gland over the sellar floor. Abnormal enhancement of the pituitary stalk was obvious with a maximum thickness of about 6 mm. There was also severe abnormal thickening and enhancement of the tentorium cerebelli with a maximum thickness of about 17 mm.
Axial T2 and post-contrast T1–weighted images of the skull base demonstrated a low T2 signal, enhancing soft tissue in the right maxillary sinus, and left cheek subcutaneous fat. In fact, axial T2 FIESTA and post-contrast T1–weighted images of the abdomen showed low T2, enhancing soft tissue around the abdominal aorta faintly infiltrating along the renal vascular pedicle, renal sinuses, and perinephric spaces leading to bilateral hydronephrosis. (Figure ).
A whole-body bone scan revealed symmetrical increased radiotracer uptake in the mandible, pelvic bones, bilateral femora, bilateral tibiae, and metatarsal bones. There was also a focus of activity in the proximal right tibial diaphysis. Myocardium plus pericardial space shadow was thickened. A bilateral dilated pyelocaliceal system was also noted. (Figure ).
A bone marrow biopsy revealed 40% cellularity as well as decreased trilineage population of hematopoietic elements that were replaced by histiocytic infiltrates exhibiting abundant foamy cytoplasm and bland-looking nuclei. Scattered eosinophils were also noted.
Flow cytometric Immunophenotypic study showed cellular bone marrow with reactive changes and a marked shift to the left at myeloid series. Immunohistochemistry study results showed CD68 (+, diffuse), Fascin (+), MPO (highlights myeloid series), CD20 (occasional scattered positive), CD3 (occasional scattered positive), TDT (no excess of blast), CD34 (no excess of blast), CD1a (-), S100 (occasional scattered positive), and Ki67 (+). (Figure ).
Therefore, considering the consensus diagnostic criteria for ECD, the diagnosis was confirmed due to xanthelasma palpebrarum, bilateral and symmetric skeletal abnormalities in the diaphyseal and metaphyseal regions of the long bones, and bone marrow biopsy findings of foamy CD68(+)/CD1a(-) histiocytes, often with admixed inflammation and fibrosis.
Vinblastine 1 mg/m2 weekly and prednisolone 50 mg daily were prescribed for the patient for 8 weeks. Following the stability of the patient's condition and improvement of the symptoms, she was discharged after 2 weeks of treatment but she was still ill. Unfortunately, she died in her town a few days after discharge due to acute pulmonary edema.


A 38-year-old Nigerian male presented three years ago (2018) with recurrent fever, oral ulcers, photosensitivity, non-scarring alopecia, and inflammatory polyarthritis involving the small joints of the hands, wrists, and elbow joints. He also had reduced urine volume and frothiness of urine. At that time, his test results were as follows: hemoglobin: 10.2 g/dL (12.0-18.5), leucocyte count: 2.04 ×109/L (4-11), platelets: 250 × 109/L (150-450), erythrocyte sedimentation rate (ESR): 106 mm/hr, and c-reactive protein (CRP): 3.2 mg/L (0-7.4). Urinalysis by dipstick revealed a protein of 3+ and hematuria. There was a positive antinuclear antibody (ANA) test with a titer of 1:640 (<1:80), anti-double-stranded DNA (anti-dsDNA): 54 IU/L (0-12), and an anti-Smith (anti-Sm) antibody. He had low levels of serum complement components: C3: 46 mg/dl (80-160), C4: 8mg/dL (15-57), and serum creatinine: 260 umol/L (57-113). Histopathologic analysis of his kidney biopsy revealed membranous glomerulonephritis, which corresponds to class V lupus nephritis.
He was then diagnosed as a case of SLE with nephritis (lupus nephritis) based on the presence of inflammatory arthritis, alopecia, oral ulcers, photosensitivity, anemia, leucopenia, raised ESR, positive autoantibody tests, hypocomplementemia, elevated serum creatinine, and biopsy-proven membranous glomerulonephritis. He was commenced on pulse methylprednisone at a dose of 1 gm/day and had a total of three doses, followed by oral moderate- to low-dose prednisolone. He was also given oral mycophenolate mofetil (MMF) at a dose of 1 gm twice daily for six months, then 500 mg twice daily, and Lisinopril at a dose of 10 mg daily. He responded favorably to treatment but was never seen again after eight months of follow-up until three years later.
In 2021, he presented to the accident and emergency department with a history of progressive bilateral weakness and pain in the lower limbs for two weeks and the inability to walk for four days. He had paraesthesia in the lower limbs and loss of sphincteric functions (bladder and bowel). There was no difficulty swallowing, diarrhea, myalgia, headache, nausea and vomiting, no blurred vision, and fever. No symptoms of the respiratory system were noted and the upper limbs were spared. There was no history of trauma, recurrent low back pain, or history of previous bladder outlet obstruction. There was no medical history of diabetes mellitus or hypertension. At this presentation, symptoms of oliguria, inflammatory arthritis, alopecia, and oral ulcers were absent. The patient, however, was still regular on MMF.
He had a temperature of 36.8°C, 98 percent oxygen saturation in room air, a pulse rate of 86 bpm, a respiratory rate of 18 breaths per min, and blood pressure of 120/80 mmHg. A neurological examination revealed normal higher cerebral function and cranial nerves. His global muscle strength in both lower limbs was grade zero (0) on the Medical Research Council Manual Muscle Testing Scale. He had reduced tone and the deep tendon reflexes of the knees and ankles bilaterally were absent. There was impaired pain and temperature sensation, two-point discrimination, joint position, and vibration sense in both lower limbs. He had a sensory level of about T10 dermatomes. The bilateral Babinski test (plantar) reflexes were flexor. He had a loss of anal sphincteric tone on the digital rectal examination. The examination of the upper limbs, cardiovascular, and respiratory systems were normal. A provisional diagnosis of acute transverse myelitis secondary to SLE was made.
His investigation results were as follows: ESR: 60 mm/hr, CRP: 2.1 mg/L (0-7.4), leucocyte count: 3.45 ×109/L, hemoglobin: 13.6 g/dL, serum creatinine: 110 umol/L, ANA: 1: 640 (< 1:80), and positive anti-ds-DNA and anti-Sm Ab. He had low levels of serum complement components: C3: 50 mg/dL and C4: 10 mg/dL. Anti-Ro (SSA), anti-La (SSB), antiphospholipid antibodies, thyroid function test (TFT), vitamin B12 assay, and serum electrophoresis were normal. Serologic tests were negative for syphilis, HIV, and hepatitis B and C. The Mantoux test was 0 mm; urinalysis, serum prostate-specific antigen, and total serum protein were all normal. The cerebrospinal fluid analysis was unremarkable with no albuminocytological dissociation. The patient was evaluated with an MRI of the spine, which revealed an expansile intramedullary T2-weighted hyperintense signal intensity within its central canal extending from the lower border of the C3 vertebrae level extending throughout its distal length (Figures , ). This confirms the diagnosis of syringomyelia coexisting with SLE previously diagnosed.
Nerve conduction studies and electromyography were not done. The patient was to continue follow-up for lupus nephritis as initially prescribed and was referred to a neurosurgeon for possible surgical intervention. However, this was yet to be done at the time of this report.


A 57-year-old male patient, a known case of diabetes mellitus type 2, presented to the emergency department with lower abdominal pain, urinary retention, lower limb weakness, and allodynia for four days before admission. One week earlier, he had experienced fever, cough, and shortness of breath, and he reported a history of contact with a COVID-19-positive patient. The patient denied any history of back trauma or receiving a new vaccination or medications. On physical examination, he was conscious, alert, and oriented to time, place, and person. In addition, the patient’s vital signs were stable. He had a sensory loss from the nipples down to the lower limbs bilaterally, along with a painful burning sensation in the same area with no skin rash or vesicular lesions noticed. There was no history of joint pain, gastrointestinal symptoms, and fecal or urinary incontinence. He had negative meningeal signs, and his cranial nerves were intact. The power in the upper and lower limbs was 5/5 and 2/5, respectively. He had decreased patellar reflex, and plantar reflex could not be assessed due to severe pain expressed by the patient in that area. The pain score from the nipples below was 5 out of 10 without touch and 10 out of 10 with touch. His Glasgow Coma Scale score was 15/15, and his urine dipstick was normal. His laboratory workup at the time of admission is presented in Table .
Complete blood count (CBC), vitamin B12, folate, and thyroid-stimulating hormone levels were within the normal range. Brain CT was normal. Therefore, an MRI spine was requested which showed an abnormal cord signal extending from the level of the D2 vertebra down to the conus medullaris, involving mainly the gray matter in the proximal thoracic cord and most of the axial cross-section of the conus medullaris and distal part of the cord (Figure ). The involvement of the gray matter was suggestive of ischemia, and the main differential diagnosis was transverse myelitis. The patient was started on 1 g intravenous (IV) pulse steroid (methylprednisolone) in the morning over three hours for seven days along with physiotherapy and strict control of his blood sugar levels. Seven days later, his condition improved, and the power in his lower limbs improved to 4/5 proximally and distally. Furthermore, the patient started to feel numbness and tingling sensation in his lower limbs. Consequently, the patient continued physiotherapy in addition to bladder training for the following month. As a part of a follow-up plan, a new MRI of the whole spine was performed to compare with the previous study obtained one month ago. On the new MRI, complete disappearance of the signal intensity was noted in the thoracic region, along with normal morphology and signal intensity without any abnormal enhancement (Figure ). The patient was discharged home with almost complete resolution of his symptoms for later follow-up in the clinic.


Here, we present a case of a 64-year-old male with a past medical history of insulin-dependent diabetes mellitus, left upper extremity deep vein thrombosis (DVT), and end-stage renal disease who underwent a deceased donor kidney transplantation approximately 16 months prior. He initially presented to an outside hospital with a five-day history of sore throat, cough, subjective fevers, fatigue, and increasing pain in his right calf. He was empirically treated for presumed pneumonia with ceftriaxone and azithromycin. At that time, coronavirus disease 2019 testing was negative. Notably, he was found to have acute thromboses in the right posterior tibial and right popliteal veins. He was initially started on a heparin infusion and subsequently transitioned to apixaban 5 mg twice a day prior to discharge home. Three weeks later, the patient presented to our outpatient transplant clinic for follow-up. At this time, he continued to endorse sore throat and cough, with a new complaint of diarrhea for the past week. Serum CMV PCR was checked and resulted in a viral load of 35,900 IU/mL. The patient was consequently admitted for CMV viremia and concern for tissue-invasive disease.
Pertinent renal transplant history includes that the donor was CMV positive and the recipient was CMV negative (D+/R-). He had completed a year of CMV prophylaxis with valganciclovir post-transplant, with his last dose about 2.5 months before his admission for CMV viremia. His home immunosuppression regimen consisted of tacrolimus 1.5 mg daily, mycophenolate mofetil 500 mg twice a day, and prednisone 5 mg daily. In addition, the patient denied a history of smoking, recent surgery, trauma, or obesity.
During the hospitalization, the patient was started on ganciclovir given the aforementioned concern for tissue-invasive disease and viremia. Complete blood count, comprehensive metabolic panel, urinalysis, immunoglobulin levels, and tacrolimus trough were unremarkable. CT chest with contrast showed non-specific right pulmonary micronodules without evidence of pneumonia. Tacrolimus was resumed, however at an adjusted dose to maintain a lower trough goal. Mycophenolate mofetil was held given the status of CMV reactivation. Prednisone was resumed at his regular home dose of 5 mg daily. The patient underwent esophagogastroduodenoscopy (EGD) and colonoscopy with biopsies that stained positive for CMV in the lower esophagus consistent with CMV esophagitis (Figure ). Ophthalmology was consulted and performed a dilated fundus examination without evidence of CMV retinitis.
Four days after starting ganciclovir, CMV PCR viral load had decreased to 1,070 IU/ml. On hospital day 7, the patient’s diarrhea resolved so ganciclovir was switched to valganciclovir 900 mg twice a day. Subsequent weekly checks of CMV PCR viral load were 120 IU/mL, then undetectable. The patient was discharged home with valganciclovir.
On outpatient follow-up, his serum CMV PCR had been undetectable on multiple occasions thus valganciclovir was discontinued after the completion of six weeks of treatment following his hospitalization. Repeat EGD two months after discharge demonstrated clearance of CMV disease in the esophagus. Additionally, the patient had been referred to hematology for further evaluation of right lower extremity DVT. Per hematology, the patient did not demonstrate any strong provoking factors for thromboembolism on history aside from his recent acute CMV infection.
This case raises the question if our transplant recipients with CMV are at higher risk for thromboembolic events and how long should the duration of anticoagulation be.


A 43-year-old female with a past medical history of uncontrolled type II diabetes mellitus, recurrent urinary tract infections (UTIs), chronic pelvic inflammatory disease (PID), abnormal colposcopy with the highest grade cervical intraepithelial neoplasia (CIN) II status post-cryotherapy, and bilateral tubal ligation (BTL) presented with worsening left lower quadrant (LLQ) pain of two months' duration. On review of systems, the patient endorsed yellow/green vaginal discharge of two months' duration without a malodor or pruritus.
The remainder of the review was negative, particularly for other gynecologic, urinary, and rheumatologic symptoms including but not limited to fever, chills, weight loss, rash, Raynaud’s skin changes, photophobia, blurred vision, dry eyes or mouth, oral ulcers, joint pain, swelling or redness, dysuria, hematuria, or urinary urgency or incontinence. The patient denied any history of autoimmune disease in herself or her family. Her only home medication was metformin. Vitals were within normal limits. Abdominal examination was significant for mild LLQ tenderness without rebound or guarding. On pelvic examination, external genitalia was normal; speculum exam revealed a well-rugated vagina with thick green discharge on the vaginal walls and cervical epithelium and a friable cervix. Pap smear was performed and was negative for intraepithelial lesions or malignancy. Bimanual examination revealed an irregular, hard, smooth, nonmobile, and tender 5-cm mass on the left anterior vaginal wall starting from the left side of the cervix and extending to the pelvic sidewall that is not connected to the cervix. No cervical motion tenderness was noted. The uterus was mobile, anteverted, and non-tender with a smooth contour. Adnexa was tender bilaterally but nonpalpable. The mass was also palpable with similar characterization, as observed through a digital rectal examination.
Transabdominal and transvaginal ultrasound (U/S) showed a complex left adnexal mass that could represent a left hydrosalpinx and/or tubo-ovarian abscess (TOA), left hydroureteronephrosis with normal-appearing right adnexa, and uterus with an endometrial stripe of 0.9 cm. A CT scan of the abdomen and pelvis revealed left hydroureteronephrosis to the level of a complex inflammatory process in the left adnexal region, possibly reflecting an evolving TOA with a trace amount of gas in the bladder and mild bladder wall thickening and perivesical fat stranding.
Labs were significant for leukocytosis of 11.2. Urinalysis (UA) was negative for leukocyte esterase, nitrites, and white and red blood cells. The wet mount was negative. Alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA) 125, B-human chorionic gonadotropin (B-HCG), chlamydia, gonorrhea, human papillomavirus (HPV), hepatitis B, hepatitis C, and HIV tests were negative. Autoimmune workup with antinuclear antibody (ANA), rheumatoid factor (RF), and anticitrullinated peptide (anti-CCP) were also negative. Blood and urine cultures returned negative as well.
Given the patient's history of PID and abnormal CIN II, we consulted gynecology. They performed endocervical curettage and endometrial biopsy, which were negative for cytologic atypia or malignancy. They later performed posterior colpotomy, cystoscopy, and diagnostic laparoscopy with peritoneal biopsy, which revealed normal pelvic anatomy with healthy ovaries, surgical absence of fallopian tubes consistent with the history of BTL, and an irregular solid hard mass in the left retroperitoneal space, not communicating with the uterus or the cervix, not visualized to be impinging on the bladder, and not visible from the abdomen on diagnostic laparoscopy. Attempts to biopsy the mass under U/S guidance were unsuccessful. They concluded the mass to be unlikely from gynecological sources. Later, an abdominal and pelvic MRI was obtained, which demonstrated a retroperitoneal mass with increased enhancement adjacent to the left ovary. A CT urogram was also done, which showed a nonspecific 4.61 x 4.41-cm soft tissue density within the left adnexa that could represent TOA or a neoplasm (Figure ).
Core needle biopsy showing storiform fibrosis and abundant plasma cells is presented in Figure , and a slide showing polarized light highlighting intense scarring is depicted in Figure .
The patient later underwent a CT-guided transgluteal biopsy of the retroperitoneal mass, which was highly suggestive of IgG4-related inflammation with microscopic evaluation showing scarring and fibrosis, which is occasionally storiform and obliterates fat, with lymphocytes, eosinophils, and plasma cells (Figure ).
The following image constitutes the most important immune slide, which shows 45 IgG4-positive plasma cells noted under a 400X field (Figure ).
There was no evidence of sarcomatoid carcinoma (negative CK AE1/AE2 stain), granulomas, or vasculitis. Serum IgG4 level was measured and found elevated at 250 mg/dL. The patient was started on broad-spectrum antibiotics for possible PID/UTI. Urology was consulted, after which a left percutaneous nephrostomy tube and left ureteral stent were placed. The patient was referred to our rheumatology clinic, after which she was started on prednisone 10 mg oral daily. One month later, she was started on azathioprine (AZT) 75 mg twice daily and received RTX 1 g IV in two doses, two weeks apart. On follow-up, the patient was found to have developed gastrointestinal symptoms likely as a side effect from AZT, which was then discontinued. She was started on methotrexate 12.5 mg subcutaneous once weekly along with daily oral folic acid. Repeat CT scan of the abdomen and pelvis about seven months after the treatment showed complete resolution of the retroperitoneal mass (Figure ).


A four-year-old male, born at full term, initially presented for brain magnetic resonance imaging (MRI) without contrast to evaluate for developmental delay, autism, and attention-deficit/hyperactivity disorder (ADHD). Images showed non-specific asymmetric prominence of the right lateral ventricle. There were no posterior fossa abnormalities. At the age of five years, the patient presented for a full spine MRI without contrast to evaluate for abnormal gait. T2-weighted images revealed a prominent central canal from the lower cervical cord and extending caudally (Figures -). A few months later, at the age of six years, the patient was evaluated in the neurology clinic for autism spectrum disorder and possible syringomyelia. History revealed the patient had a tip-toe gait and a general lack of coordination. Other than gait abnormality, the neurologic examination was non-focal. The patient was diagnosed with syringomyelia, and a follow-up full spine MRI with and without contrast was performed six months later. The images from that time showed a similar prominent central canal measuring 0.5 mm in the lower cervical cord, 1 mm in the thoracic cord, and 2 mm in the distal cord, which ended at L1-2. There was no evidence of malignancy. On the same day as this imaging, the patient was evaluated in the neurosurgery clinic for thoracolumbar syringomyelia. No new symptoms were noted. The patient was diagnosed with holocord hydromyelia. Follow-up imaging was ordered, and a physical therapy consultation was arranged. A year and four months later, the patient was again evaluated in the neurosurgery clinic. The patient continued to have balance problems and difficulty in walking but had developed no new symptoms. The neurological exam was again non-focal, except for tip-toe gait. The patient was diagnosed with thoracolumbar syringomyelia. Follow-up imaging was ordered, and an orthotics consultation was arranged. Almost a year later, at eight years of age, the patient underwent a full spine MRI with and without contrast. Imaging findings were normal; specifically, the central canal was no longer prominent at any level (Figures -).


This case report describes the course of a 67-year-old White Swiss male patient diagnosed with PD and MS who visited our rehabilitation hospital for intensive neurorehabilitation two times within 1 year.
The patient lives with his wife in a flat. He worked as a consultant in a private company before his disease symptoms, especially fatigue and muscle weakness (tetraparesis due to MS), forced him to retire 21 years ago (in 1999). The patient was a recreational musician, but stopped his activities because of the disease-related impairments, including manual dexterity. Currently, he likes listening to audiobooks and he enjoys doing administrative work for his family and neighbors. He used to attend a support group for people with MS, but quit some years ago. The patient reports no other structured social activities except for close contact to his family, friends, and neighbors.
The following diagnoses have been confirmed at hospital admission in October 2019 and in May 2020:Parkinson’s disease of the akinetic–rigid subtype and with left-sided predominance. Disease severity as rated with the Hoehn and Yahr scale was 4 out of 5 []. The first PD-specific medication was prescribed in 2015. Relapsing–remitting multiple sclerosis with a secondary progressive course. First MS-specific medication in 1988, confirmed diagnosis in 1992. The last relapse took place in June 2016. Diabetes mellitus type 2. Arterial hypertension. Urinary retention and incomplete bladder emptying. State after right-sided L3 pain syndrome due to a foraminal/extraforaminal disc hernia at lumbar vertebrae 3/4. Microsurgical herniotomy L3 on the right side in September 2011.
The main symptoms of the patient were related to PD, MS, and his low back pain syndrome. Clinical examination revealed bradykinesia of the limbs, while no significant rigidity or rest tremor were observed. The patient reported motor fluctuations including off-periods and dyskinesia. He featured a complex gait disorder with hypokinetic and spastic–ataxic elements. Besides, he suffered from postural instability and freezing of gait episodes. The main physical MS-specific symptoms were tetraparesis, fatigue, and trouble with sensation and coordination. The main activity limitations were related to mobility (transferring, walking stability, walking endurance, stair climbing, balance).
The patient received a combination therapy consisting of levodopa/benserazide (Madopar LIQ 62.5, Madopar DR 250), levodopa/carbidopa/entacapone (Stalevo) and pramipexole (Sifrol ER) for treatment of PD. During the first reported stay in our hospital, the daily dosage of levodopa was reduced by 150 mg. During the second stay, daily dosage of levodopa was increased by 150 mg and that of pramipexole by 0.75 mg. Motor fluctuations improved by the adjustments of the pharmacological therapy. The MS-specific medication consisted of 44 μg interferon beta-1a (Rebif) three times per week and has been unchanged for several years.
Since the patient was diagnosed with PD in 2015, he had visited our clinic already several times for intensive inpatient rehabilitation, as prescribed by his general practitioner.
The complete timeline of the patient is illustrated in Fig. .
On 4 September 2019, the patient fell and fractured three ribs on the right side. The fractures were treated conservatively, but within the following weeks, the patient experienced significant deterioration in physical functioning, mobility, and functional independence. Thus, he presented to his general practitioner who referred him for intensive inpatient rehabilitation to our neurological rehabilitation hospital. The patient visited the hospital for 4 weeks, starting 13 October 2019 until 9 November 2019. He was discharged home and referred to regular outpatient physiotherapy two times per week.
From 10 November 2019 on, the patient lived in his home and participated in the prescribed regular outpatient rehabilitation. On 16 March 2020, a lockdown was federally directed in Switzerland owing to the COVID-19 pandemic, including severe restrictions on outpatient rehabilitation services. Physiotherapy practices were only allowed to offer very limited outpatient services during the lockdown. Physiotherapy interventions for chronic neurological conditions were not considered “urgent” and usually not allowed during the lockdown. Thus, the patient paused his outpatient rehabilitation for 6 weeks. Over this period of time, the patient experienced significant deteriorations in physical functioning and functional independence.
On 27 April 2020, outpatient physiotherapy services and practices were allowed to reopen, and on 5 May 2020, the patient had his first physiotherapy session after the start of the lockdown. He had two physiotherapy sessions per week, but failed to regain his functional abilities that he lost during the COVID-19-related interruption of his rehabilitation process.
The patient reattended our hospital for intensive inpatient rehabilitation, starting 25 May 2020 and ending 19 June 2020 (4 weeks). After discharge, the patient received outpatient physiotherapy services two times a week. We did not follow up the patient after discharge.
At hospital admission, the patient was assessed with a broad set of generic and disease-specific measures of physical functioning and mobility as part of the physiotherapy treatment. All assessments were performed during the on-state. The clinical outcome assessments are described in the following section.
The first inpatient rehabilitation stay (4 weeks) was prescribed to improve the patient’s mobility, walking distance, and physical functioning; to reduce fall risk and fear of falling; to improve disease-related symptoms and activity limitations such as MS-related fatigue and PD-related start hesitations; to learn cuing strategies to deal with freezing of gait episodes; to increase quality of life; and to improve functional independence in the activities of daily living.
In the rehabilitation hospital, the patient received multimodal, interprofessional, and intensive rehabilitation, according to clinical practice guidelines [, ] and accompanied by medical, social, and nursing care. The rehabilitation modalities scheduled during this inpatient stay are listed in Table . Usually, a therapy session was scheduled for 30–45 minutes. On each weekday, the patient was scheduled for three to six interventions, either in single or group-based sessions. Most physical interventions, including physiotherapy, exercise training, and resistance training, were prescribed to improve mobility, balance, ambulation, lower extremity muscle strength, physical functioning, and functional independence. Occupational therapy was prescribed to improve functioning in daily life and dexterity of the upper limbs. Neuropsychological training aimed to improve cognitive abilities related to the patient’s functioning in daily life.
Regular outpatient physiotherapy was performed two times a week (30-minute session each) to maintain and improve physical functioning, mobility, balance, quality of life, and functional independence in the activities of daily life. The reduction of the patient’s low back pain was a further objective of the prescribed physiotherapy. The main treatment modalities were exercise and resistance training for the lower limbs and the trunk, balance training, massages, manual therapy interventions for the back and shoulders, and gait training, as reported by the outpatient physiotherapists. The selection of modalities was subject to the participant’s current needs and abilities. In addition, the patient performed regular gait training with his wife.
During the lockdown, the patient did not receive any professional rehabilitation interventions, but continued gait training with his wife frequently.
The second inpatient rehabilitation stay (4 weeks) was prescribed to improve the patient’s safe ambulation, mobility capacity, balance, and functional independence, and to regain the functional level that he had prior to the COVID-19-related therapy break. Similar to the first hospital stay, the patient received multimodal, interprofessional, and intensive rehabilitation, according to clinical practice guidelines [, ]. The extent of rehabilitation modalities scheduled during this inpatient stay is listed in Table . The interventions were prescribed to achieve the patient’s functional goals as described above (first inpatient rehabilitation stay). The medication was not changed during the time between the two inpatient rehabilitation visits.
Within the regular hospital physiotherapy care, a set of functional outcome assessments was performed with the patient on admission and discharge. During the second inpatient stay, some outcome assessments were repeated weekly to better describe the rehabilitation course. The physical outcome assessments and the patient’s assessment scores are listed in Table .
Mobility capacity was assessed with the de Morton Mobility Index (DEMMI; Fig. ) [–], the Hierarchical Assessment of Balance and Mobility (HABAM, Fig. ) [, ], and the mobility subscale of the Barthel Index (Fig. ) []. According to those three outcome assessments, the patient experienced improvements in mobility capacity during the first rehabilitation stay, which deteriorated or remained unchanged over the pandemic-related interruption of outpatient rehabilitation. However, mobility capacity improved over the second hospital stay by 17% (DEMMI), 50% (HABAM), and 20 points (Barthel Index mobility subscale). These improvements are beyond the measurement error of these assessments reported for older adults and can be considered clinically relevant [, , ].
Ambulation was assessed with the functional ambulation categories (FAC; Table ) []. At hospital admission after the COVID-19-related therapy break, the patient was mobile in a wheelchair for longer distances, but he could only walk for short distances with a rollator and intermittent support of one person to help with balance and coordination (FAC 2). At discharge, he was able to walk independently with the rollator within the hospital for shorter distances (< 300 m; FAC 4). However, with two crutches (his preferred walking aid) the patient needed stand-by assistance from another person (FAC 3).
Walking endurance was assessed with the 6-minute walk test []. As seen in Table , the patient improved his walking distance within 6 minutes by 102 m (improvement of 268%) and by 98 m (109%) over the first and second rehabilitation stay, respectively. Figure illustrates how the patient deteriorated in the 6-minute walk test after the therapy interruption but then regained his former walking endurance. This improvement can be considered clinically important [].
Gait speed values (10-meter walking test) of the patient over time are illustrated in Fig. . The patient improved by 77% over the first inpatient rehabilitation stay, decreased back to his former ability (0.29 m/second) after the rehabilitation interruption and re-improved by 131% to a gait speed of 0.67 m/second. This value is still very low compared with normative values of older people [], but the amount of change can be considered clinically important [].
In addition, we conducted some disease-specific assessments that were not part of standard clinical routine. To assess the level of fatigue, we conducted the Fatigue Severity Scale, a patient-reported outcome assessment []. However, no relevant changes were observed in the patient, who reported “substantial fatigue” according to the scale score of 6.7 points []. MS-specific disability was assessed with the Expanded Disability Status Scale (EDSS). We did not observe any alterations in EDSS status of the patient, since he required constant bilateral support to walk 20 m without resting at all times (EDSS score of 6.5). Quality of life was assessed with the PD-specific Parkinson's Disease Questionnaire (PDQ-39) [] and did not change substantially over time.
We do not have sufficient information or objective measures of the patient’s physical functioning or assessment scores prior to hospital admission in October 2019 or from the outpatient physiotherapy. We do not report any assessment scores from other rehabilitation disciplines, such as speech and language therapy or nutritional therapy.
At hospital discharge in November 2019, the patient was able to walk independently with a rollator within his domestic environment, and he was able to ambulate with two crutches when guided by his wife or another person. The maximum walking distance with two crutches was 605 m, which he was able to complete continually within 23 minutes.
The rehabilitation goals for the second inpatient stay were directed by the patient, who aimed for independent ambulation within his house with a walking aid. In addition, the patient enjoys walking with crutches and he reported to aim at “a better gait stability and a long walking distance with crutches.” Since the patient explicitly wished to “regain his pre-pandemic functional abilities,” the mobility-related rehabilitation goals were subjected to the patient’s functional abilities prior to the pandemic and defined as:Intermediate goal: After 2 weeks of rehabilitation, the patient walks independently with a rollator in the hospital (FAC score of 4). Discharge goal 1: At hospital discharge, the patient walks independently with a rollator in the hospital (FAC score of 4) and the patient is able to walk with two crutches under stand-by assistance (FAC score of 3). Discharge goal 2: At hospital discharge, the patient can walk up to 600 m continually with two crutches (no limitation of time defined).
The patient failed to reach the intermediate rehabilitation goal. Two weeks after hospital admission, he still needed stand-by assistance when he walked with a rollator within the hospital. Concerning discharge goal 1, the patient was able to walk for 200 m with two crutches and stand-by assistance or for 300 m with a rollator independently (goal achieved). He failed, however, to reach the discharge goal 2 since he did not reach the maximal walking distance of 600 m with two crutches.


In November 2020, a 75-year-old male with low comorbidity (hypertension, no previous abdominal surgery) was admitted to the Department of General Surgery, Frieri-Criscuoli Hospital (Avellino, Italy) with abdominal pain, vomiting and bowels not opened in the last 3 days. The patient lived in a rural area of the Campania region, southern Italy. The anamnesis revealed that until 3 years ago he had an orchard and raised chickens and pigs for his own consumption. Physical examination revealed abdominal pain with bloating. Examination of blood showed a white blood cell (WBC) count of 19.16 × 103/μL with 86.8% neutrophils and 2.9% eosinophils. Computed tomography (CT) scan exposed multiple air-fluid levels in the epigastrium and left hypochondrium with some fluid in mesenteric recesses and signs of bowel obstruction (Fig. ). The day after the hospitalization, the symptoms persisted so the patient was referred to surgery. The explorative laparotomy revealed bowel dilatation with vascular suffering and kinking of a tract of ileus in correspondence of a severe mesenteric inflammation. During the bowel palpation, from the Treitz ligament to the ileocecal valve, a long worm-like foreign body was felt and this occasioned to a little enterotomy to extract the worm (Fig. ). The palpation of the entire bowel did not show the presence of other ones. The worm recovered was washed in saline solution and stored in 70% (v/v) ethanol. A stool sample was also collected from the bowel of the patient and preserved at + 4 °C.
The worm and the stool samples were sent, within 24 h, to the laboratories of the WHO Collaborating Centre for diagnosis of intestinal helminths and protozoa (WHO CCITA-116, University of Naples Federico II, Italy) for further analysis.
The worm was cylindrical in shape, pinkish in colour and measured 20 cm in length and 6 mm in diameter (Fig. ). Under the stereomicroscope the helminth presented a buccal orifice with three lips (two subventral and one dorsal) and a straight posterior end (Fig. ). The worm was identified as an adult female of Ascaris spp. [].
A portion of the adult worm was sent in 70% (v/v) ethanol to the Department of Public Health and Infectious Diseases, Section of Parasitology (Sapienza University of Rome, Italy) for the genetic characterization.
DNA extraction was performed using the Isolate II Genomic DNA kit (Bioline, UK), according to the manufacturer’s protocol. The entire ITS nuclear region (ITS1, 5.8S, ITS2) was amplified using 20 ng of genomic DNA, 10 mM Tris–HCl (pH 8.3), 1.5 mM MgCl2 (Bioline), 40 mM of a nucleotide mix (Bioline), 20 pmol/µl each of the forward primer NC5 (59-GTAGGTGAACCTGCGGAAGGATCAT- 39) and the reverse primer NC2 (59-TTAGTTTCTTCCTCCGCT-39) described by Zhu et al. [] and 1.0 U of BIOTAQ DNA Polymerase (Bioline) in a final volume of 50 µl. The PCR was performed in a GenePro Eurocycler Dual Block (Bioer) under the following conditions: 10 min at 95 °C (initial denaturation), 30 cycles of 30 s at 95 °C (denaturation), 40 s at 52 °C (annealing) and 75 s at 72 °C (extension), and a final elongation step of 7 min at 72 °C. A negative control (PCR master mix without genomic DNA) was included in the amplification reaction.
A PCR product of around 1000 bp was obtained. The ITS amplicon was digested with the restriction endonuclease HaeIII, as the resulting patterns have been previously proved useful for the identification of Ascaris species. This approach yielded the specific banding pattern peculiar to the A. suum genotype, showing three bands of about 610 bp, 230 bp and 140 bp (Fig. ).
The stool sample was analysed with the FLOTAC dual technique [] as described in Gualdieri et al. []. The analytic sensitivity was four eggs per gram (EPG) of faeces. Faecal examination revealed the presence of unfertilized Ascaris eggs (Fig. ) with an intensity of 16 EPG.
The patient was treated with mebendazole 100 mg twice a day for 3 days. The stool examination at 7-days follow-up was negative. The post-operative hospitalization was regular with re-alimentation after 3 days and discharge after 12 days, asymptomatic. A week after the discharge another parasitological stool examination was negative.


A 63-year-old man was admitted to our hospital because of fever, abdominal pain and hematochezia for 2 months. He was treated with broad-spectrum antibiotics (ceftizoxime and imipenem) in local hospital. However, symptoms aggravated along with persistent diarrhea. One week later, he was transmitted to our hospital. Nine months before admission, the patient was diagnosed as MDS-RAEB2 and received 4 courses of azacytidine and micro-transplantation. The number of primitive cells in bone marrow declined from 25 to 5% after 4 courses of treatment. There was no family history of autoimmune diseases or inflammatory bowel disease.
On admission, he was conscious and anemic. There was tenderness on palpation of the right lower quadrant with mild rebound pain. Blood tests showed that white blood cells count was 13 × 109/L, hemoglobin level was 82 g/L, platelet count was 93 × 109/L. Erythrocyte sedimentation rate was 53 mm/h (reference, < 18 mm/h), high sensitivity C-reactive protein was 247 mg/L (reference, < 3.1 mg/L). Fecal calprotectin was 872 μg/g.
The computed tomography enterography (CTE) (Fig. ) showed bowel wall thickening and mural hyperenhancement of terminal ileum and cecum. Gastroscopy (Fig. A, B) revealed multiple erosions in stomach. Colonoscopy (Fig. C–F) showed multiple round ulcers in terminal ileum and ileocecal valve and multiple yellow dotted pseudomembranous attachments throughout colon. Capsule endoscopy also revealed multiple irregular ulcers in lower ileum. Histological analysis showed partially thickened with hyaline degeneration in the wall of small blood vessels.
During multidisciplinary team meeting, diagnosis and differential diagnosis was discussed as infectious colitis, cytotoxic drug-related intestinal ulcer, BD, Crohn's disease and intestinal tuberculosis, etc.
Firstly, stool samples, blood samples and previous colonoscopy biopsy specimen were sent to the laboratory to be tested for infection (including bacteria, tuberculosis, virus and fungus). Intriguingly, the clostridium difficile toxin A and B in stools was positive and clostridium difficile infection was confirmed. The patient received vancomycin 125 mg 4 times per day orally []. The fever and diarrhea relieved soon after medication. The test of clostridium difficile toxin A and B were negative after two weeks treatment. Colonoscopy showed that the pseudomembrane disappeared but the intestinal ulcers have no tendency to shrink (Fig. ). Thus, opportunistic infections not enough to explain the whole state of the symptoms.
Secondly, azacytidine has been reported to induce hematochezia and intestinal ulcer in literature. Since our patient's symptom occurred between the 3rd and 4th course of azacytidine, we assessed the relationship between azacytidine and intestinal ulcer in our case. According to literature, the intestinal ulcers induced by azacytidine occurred shortly after medication and relieved 7 to 20 days after stopping the medication. [] However, the intestinal ulcers of our patient existed 54 days after last course. The Naranjo adverse drug reaction probability score of this patient is suspicious (2 scores) which not enough to confirm the diagnosis of drug-related bowel disease.
Recently, studies show that trisomy 8 positivity MDS with Behçet’s-like disease often performed as gastrointestinal ulcers. The bone marrow cells analysis of this patient showed a karyotype of 47 XX, + 8 (Fig. ) accompanied with BCOP, IDH1, PHF6 and RUNX1 gene mutation. Detailed inquiry of medical history revealed epifolliculitis and frequently recurrent oral ulcers 2 months before admission. Based on the International Criteria for BD [] which point score system that scoring ≥ 4 indicates BD, this patient scored 4. Above all, a diagnosis of trisomy 8 positivity MDS with BD was considered. The patient received glucocorticoid for BD along with the 5th course of azacytidine. Symptoms relieved and follow-up endoscopy (Fig. ) showed significantly improved intestinal ulcer 2 months after treatment with glucocorticoid.


A 44-year-old male initially presented with pain in his lower extremity. He visited a nearby hospital that referred him to our institute where a working diagnosis of a bone tumor was made. The plain radiograph shows an osseous lesion on the left posterior pelvis. Computed tomography (CT) depicted an osseous lesion arising from the left sacral ala. The osseous lesion was covered by a layer with intermediate signal intensity on the T1 weighted image and high signal intensity on the T2 weighted image from magnetic resonance imaging. The diagnosis from the image was an osteochondroma, which was covered by a cartilaginous cap. The maximum size of the tumor was ~6 cm and the thickness of the cartilaginous cap was <2 cm (). The histology of the needle biopsy of the cartilaginous cap showed a proliferation of chondroid tissue without atypia, suggesting an osteochondroma.
On diagnosis of the osteochondroma, a resection was performed. With the patient in the lateral position, a skin incision was made along the iliac crest to the contralateral paravertebral muscle, with a distal convex shape at the sacrum. The distal multifidus muscle was detached from the lamina of the sacral and lumber vertebrae. The posterior ilium and vertebrae were exposed, and the tumor was resected. Following resection, a vertebral fusion between L5 and S1 was performed using pedicle screws (). No complications associated with the operation appeared. The pathological diagnosis of the resected material was osteochondroma. The patient was able to walk without a crutch though dull back pain existed 6 months after the surgery with the degree of the pain getting worse. Image analysis 11 months after the initial operation revealed new cartilaginous nodules. The distal multifidus muscle on the tumor side was still thin, but the distal multifidus muscle on the non-tumor side was morphologically almost normal ().
A needle biopsy of the new tissue revealed no atypical cartilaginous tissue. However, taking into consideration the clinical course, chondrosarcoma was diagnosed. Surgery was performed with almost the same incision, but the incision was extended to the distal sacrum (). The multifidus muscle was removed from the distal sacrum in the same way as in the primary operation (). The tumor compressed the L5 nerve root and was resected in several blocks. The pathological diagnosis of the resected material was a chondrosarcoma arising from the osteochondroma (). The pain was relieved postoperatively.


A 2-month-old male domestic shorthair cat was presented to a local veterinary clinic with a complaint of recurrent generalized convulsions. The local veterinarian noticed the cat also had frequent facial twitching, ataxia, visual impairment, and slightly decreased mentation at the first consultation. Video clips recorded by the owner () showed generalized myoclonic seizures, which was momentary but clustered for 1 to a few minutes, and GTCS lasting about several tens of seconds to 1 minute. These seizures were initially observed several times per week; therefore, antiseizure drug (ASD) therapy with 1.0 mg/kg of phenobarbital (PB) every 12 h per os was initiated. The dose of PB was increased to 2.0 mg/kg q12h PO (achieved static serum level: 14.8 μg/ml) at 3 months of age due to insufficient seizure control. At this time, complete blood count, serum chemistry including fasted and postprandial ammonia and total bile acid, urinalysis, screening test of feline immunodeficiency virus and feline leukemia virus, cerebrospinal fluid (CSF) analysis including PCR for Toxoplasma gondii and feline corona virus, and low-field (0.4T) magnetic resonance imaging (MRI) of the brain were performed. All complementary tests were unremarkable. Due to severely increased seizure frequency to > 40 times daily (uncountable), the dose of PB was further increased (4.0 mg/kg q12 h PO), and zonisamide (8.0 mg/kg q12h PO), diazepam (DZP; 0.5 mg/kg q12 h PO) as well as levetiracetam (LEV; 20 mg/kg q8 h PO) were added. However, zonisamide was discontinued 3 days after the initiation due to the appearance of aphagia.
At 5 months of age, the cat was referred to a veterinary neurologist (SK) at the Veterinary Specialists Emergency Center (Saitama, Japan). Neurological examination revealed severe mental dullness, disorientation, difficulty in standing and walking, decreased postural reactions in all limbs, and bilateral menace response deficits with normal pupillary light reflexes. Appetite remained normal but the cat needed assisted feedings. Levetiracetam had been discontinued by the owner because the cat seemed to develop stupor after its administration. Doses of PB and DZP were maintained at 5.0 mg/kg q12 h PO (achieved static serum level: 27.1 μg/ml) and 0.8 mg/kg q12 h PO, respectively. Although the frequency and duration of GTCS decreased, myoclonic seizures and short tonic seizures still occurred 1–6 times per day (sz/d). Although other differential diagnoses at this point including inborn errors of metabolism, inherited neurodegenerative conditions, or immune-mediated limbic encephalitis could not be completely ruled out, further diagnostics such as the Tandem mass spectrometry and/or investigation of known antibodies such as anti-voltage-gated potassium channel and/or anti-leucine-rich glioma inactivated 1 receptor antibodies for limbic encephalitis were unavailable locally then. At 7 months of age, the cat was presumptively diagnosed as DRE of unknown cause with severely impaired quality of life (QOL), when the potential candidacy of the epilepsy surgery research project was discussed and the owner requested the candidacy to be evaluated.
The project team of veterinary epilepsy surgery () discussed this case based on the abovementioned history and data. All members considered this cat as a candidate for epilepsy surgery. Electroencephalography (EEG) and high-field MRI as presurgical evaluations were performed to determine the type of surgical procedure.
At 8 months of age, the cat was further referred to the Veterinary Medical Teaching Hospital of Nippon Veterinary and Life Science University (Tokyo, Japan) to undergo EEG and high-field MRI. At this point, seizure frequency increased reaching up to 7–10 sz/d, including GTCS. The cat was non-ambulatory and nearly stuporous but remained responsive to forced feeding, loud sounds, and nociceptive stimulation. Postural reaction deficits and bilateral menace deficits were noticed on neurological examination; no other abnormalities were recorded. Feeding, drinking, and urination had been fully assisted by the owner. Complete blood count and serum chemistry profile were re-evaluated and revealed mild dehydration, which was easily improved later by increasing the water intake. Scalp EEG under sedation () revealed frequent spikes and multiple spike complexes were observed on the central regions (C3, C4, Cz) dominantly but synchronized generally (). High-field MRI (3.0T) under general anesthesia () showed no appreciable structural abnormalities in the whole brain (). Cerebrospinal fluid analysis including cell count (0/μl; ref 0–5/μl), cytology (no cells observed), protein concentration (12.4 mg/dl; ref 0–25 mg/dl), glucose (126 mg/dl; ref 35–140 mg/dl), and electrolytes (Na+ 158; K+ 2.9; Cl− 135 mEq/l) was also unremarkable. The serum level of PB at this point was 33 μg/ml. With these repeated MRI and CSF analysis, inherited neurodegenerative conditions were considered unlikely. Although other differentials could not be completely ruled out, DRE of unknown etiology was considered the most likely.
Based on these results, the epileptogenic zone of this case was not determined; therefore, the project team selected CCT as a suitable surgical procedure based on the following reasons: (1) epileptiform discharges distributed bilaterally; (2) unremarkable MRI; (3) severe seizure frequency that might result in decreased mental status; and (4) decreased QOL of the patient and the owner (). As the final checkpoint to detect an identifiable epileptogenic focus, an intraoperative electrocorticography (ECoG) recording was planned immediately following the craniotomy. If the intraoperative ECoG recording clearly identified the epileptogenic focus, a different procedure such as a focal resection and/or multiple subpial transections would have been considered more suitable ().
The owner was requested to record seizures including the types, frequency, and duration, as well as the visual analog scales (VAS; ) before and 3, 6, and 12 months after surgery. An attending neurologist (DH) evaluated the activities of daily living (ADL) () and performed follow-up EEG and MRI during the same period.
Corpus callosotomy (CCT) was performed at 12 months of age. General anesthesia was induced by propofol (6 mg/kg IV) and maintained with inhalation of isoflurane and oxygen. The cat was positioned in sternal recumbency in a Sphinx-like position. During surgery, electrocardiogram, oxygen saturation, end-tidal CO2 concentration, indirect blood pressure, rectal temperature, and urine production volume were monitored. Lactated Ringer's fluid was infused at 3–5 ml/kg/h, and a constant rate infusion (CRI) of remifentanil as intraoperative analgesia was performed at 20 μg/kg/h. After shaving and sterilization, an H-shaped scalp incision was made with the skin opened like a double door. Bilateral temporal muscles were incised along to the external sagittal crest and detached from the parietal bones, and then retracted bilaterally. A 3 cm (left–right) × 4 cm (rostral–caudal) rectangular-shaped craniotomy straddling the left and right of the parietal bone was performed. The first four burr holes were made on each corner of the rectangle with the rostral pair at the level of the caudal end of the frontal bone and the caudal pair approximately 1.5 cm rostral to the external occipital protuberance. The craniotomy was completed by connecting these burr holes to expose the underlying cerebral surface of the parietal lobes. In the process of connecting the burr holes, the craniotomy lines connecting the two rostral and the two caudal burr holes, i.e., transverse craniotomy lines, had widened areas across the midline in order to visualize the underlying dorsal sagittal sinus well. The removed bone fragment was wrapped with saline-filled gauze and saved for the closure.
After the craniotomy, epidural ECoG was recorded. A 1.5 × 1.5 cm grid-type silicon-sheet electrode with nine exploration electrodes was placed on the dura covering each hemisphere's parietal lobe. On ECoG, bilaterally synchronized spike-containing burst-suppression was recorded ().
As ECoG did not aid to identify the epileptogenic zone, a sagittal sinus-based U-shaped dural incision was made on the left hemisphere and inverted to the right side. The left hemisphere was gently retracted laterally with neurosurgical putties, spatula, and shafts of suction to widen the longitudinal fissure. By peeling off the cingulate gyrus on both sides under the falx gently, the bright white CC was exposed ().
The CC was bisected using bipolar cautery and suction from the caudal, the splenium, to the rostral, the genu. During the bisecting of the CC, the great cerebral vein, where the confluence of the vein of the corpus callosum and internal cerebral vein, was observed at the caudal end of the splenium. The third ventricle was also observed under the body. During the approach of the genu, a cortical vessel on the cingulate gyral surface was damaged, and the hemostasis manipulation and the subsequent brain swelling made it difficult to identify the genu. Therefore, the rostral dissection was abandoned (). Due to the brain swelling, 1 g/kg of mannitol was intravenously administered over 15 minutes.
The dura was sutured with 6-0 polydioxanone after confirming normalized brain volume and no bleeding from the intracranial surgical field. Then, a post-callosotomy intraoperative ECoG was recorded; Although large spikes were still synchronized on both hemispheres, small independent spikes, not seen pre-CCT, were observed from each hemisphere (). After recording ECoG, the stored bone fragment was returned and fixed with polymethylmethacrylate. Temporal muscles and scalp were sutured routinely. A percutaneous endoscopic gastrostomy (PEG) tube was placed to facilitate postoperative feeding.
The cat recovered from anesthesia uneventfully, and the patient's conscious level had moderately improved compared with the preoperative state. However, facial twitching was observed intermittently until the next day. As postoperative analgesia, CRI of fentanyl (2 μg/kg/h to tapered) was infused for 12 h after surgery, and a fentanyl patch (4.2 mg/head) was applied for 3 days. Although cefmetazole (25 mg/kg q2–12h IV) had been used from intra- to postoperative 12 h, the cat showed fever (~40°C) with mild neutrophilia (WBC 22,000 /μl) on the next day. Because bacterial meningitis was a potential concern, meropenem (25 mg/kg, CRI for 30 min q24h) for 3 days and enrofloxacin (5 mg/kg q24h PO) for 5 days were administered. The fever ceased within 4 h after initiation of meropenem, after that fever and leukocytosis had never been observed remaining the cause being unidentified.
The day after surgery, the cat was able to maintain a sitting position and eat wet food on his own, with the nutritional requirement maintained using a PEG tube. Furthermore, on the postoperative day (POD) 3, even though mild right-sided hemiparesis was observed, the cat became ambulatory and was able to voluntarily urinate and defecate. The PEG tube was removed at POD 10, and the cat was discharged from the hospital at POD 16. During the postoperative hospitalization, 5 myoclonic seizures were observed, while there were 12 seizure-free days. Neurological findings at the discharge time were slightly somnolence, mild disorientation, ambulate but generalized ataxia with postural reaction deficits in all limbs, and loss of biliteral menace response. Phenobarbital (3.5 mg/kg q12 h PO) and DZP (0.5 mg/kg q12 h PO) were continued throughout the hospitalization.
After discharge, the cat was routinely consulted at a local clinic every 2–4 weeks, and presented to the teaching hospital at 3, 6, and, 12 months after surgery for rechecks and follow-up EEG and MRI. Antiseizure drug therapy with PB and DZP were maintained for the 1-year follow-up period. The neurological status, mild cognitive impairment, ataxia with decreased postural reactions, loss of bilateral menace response, remained unchanged for the 1-year follow-up period. Mental status fluctuated from alert to somnolent depending on the time of the visit or seizure frequency. Changes of seizure types were observed postoperatively: GTCS had completely disappeared, and generalized myoclonic seizures changed to momentary facial myoclonic seizures and shorter tonic seizures. On the other hand, a new seizure type manifesting as the initial left arm-extended fencing posture (fencing posture seizure; FPS) followed by contralateral (right) myoclonic or clonic seizures () emerged 7 months postoperatively. Sequential changes in seizure frequency, VAS, and ADL from the preoperative time to the 1-year follow-up are shown in , , and , respectively. Seizure frequencies of all seizure types were markedly decreased (7.2–1.7 sz/d; 76% reduction); however, 1–2 sz/d in average either myoclonic seizures or FPS, or both remained unchanged through the 1-year follow-up period.
Follow-up scalp EEGs showed clearly decreased spike frequency. Although a few spikes were observed in a hemisphere only, most were still synchronized bilaterally (). Follow-up MRI at 3, 6, and 12 months after surgery revealed the bisected CC with the remaining genu, loss of caudal part of the left cingulate gyrus, and old hemorrhagic and a necrotic lesion in the left cingulate gyrus likely related to intraoperative tissue handling as well as vascular damage ().


A 71-year-old female suddenly experienced the left lower extremity pain and altered urethral sensation after backward bending. Despite conservative treatment by a local physician and urological physician, her symptoms progressed to urinary hesitancy and anal sphincter dysfunction. She was admitted to our hospital 11 days after the initial onset of altered urethral sensation. MRI and myelography revealed a central LDH with central migration at L5/S1 and lumbar spinal stenosis with degeneration. We performed decompression 17 days after the initial onset of altered urethral sensation. The decompression was conducted via bilateral laminectomy and discectomy. Though there was a gradual improvement in urinary hesitancy and anal sphincter dysfunction at three months, the altered urethral sensation has remained at two years postoperatively.


A 38-year-old female had chronic lower back pain and right leg pain, which was managed conservatively by a local physician. After several months, the patient experienced an acute exacerbation of the lower back pain and right leg pain. The patient noticed an altered urethral sensation one week later, and so she sought medical attention from an emergency physician. The next day, the emergency physician referred the patient to us for evaluation of a possible neurogenic bladder. At the time of presentation to our department, the lower back pain and right leg pain were relieved. On examination, there was no weakness in the lower extremities. The patient had altered urethral sensation in the absence of urinary hesitancy, and the rectal tone was normal. MRI revealed a massive central herniated disc at L5/S1 that was severely compressing the dural sac. We performed emergency decompression one day after the initial onset of altered urethral sensation. The decompression was conducted via bilateral laminectomy and discectomy. After surgery, there was a gradual improvement in the altered urethral sensation, and this was fully resolved at three months postoperatively.


A 37-year-old male had been experiencing low back pain and right sciatica for a week and was rushed to our hospital after experiencing pain progression and altered perirectal sensation. MRI revealed a central LDH with central migration at L4/5. The initial decompression was conducted via microendoscopic discectomy. Despite the surgery, there was no improvement in symptoms before surgery. Postoperative MRI residual revealed herniation, and we strongly recommended performing a second surgical decompression. It took several days to obtain consent for surgery because he desired conservative treatment. His symptoms progressed to urinary hesitancy and loss of anal sphincter function during the period before he consented to surgery. Finally, the complete decompression was conducted via bilateral laminectomy and discectomy 18 days after the initial onset of altered perirectal sensation. Urinary hesitancy and loss of anal sphincter function were residual at three months postoperatively. Though these symptoms recovered two years after surgery, altered perirectal sensation remained.


A 41-year-old male had chronic lower back pain, which was managed conservatively by a local physician. Though he once experienced relief of the symptom improvement, he had low back pain again, as well as left lower extremity pain, diminished perineal sensation, and delayed micturition after several months. A few days after the onset of these symptoms, he visited our hospital. MRI revealed a central LDH with central migration at L5/S1 and lumbar spinal stenosis with degeneration. We performed decompression six days after the initial onset of diminished perineal sensation and delayed micturition. At the time of surgery, decreased desire to void and anal sphincter dysfunction had appeared. The decompression was conducted via microendoscopic laminoplasty and discectomy six days after the initial onset of diminished perineal sensation and delayed micturition. Though there was a gradual improvement in decreased desire to void and anal sphincter dysfunction at three months, the diminished perineal sensation has remained at two years postoperatively.


A 16-year-old girl presented with declining motor function of the right hand over the last four years. She complained of reduced force, loss of fine motor skills and episodes of painful muscular cramps. Clinical examination showed athetotic finger movements at rest. Painful contractions were provoked by performing tasks. Muscular atrophy was noted. Finger tapping test confirmed loss of fine motor control and augmented reflexes were found in the arm. The movement disorder was clinically described as a unilateral hand dystonia (with phasic and tonic components) combined with upper motor neuron syndrome (muscle weakness, hyperreflexia and reduced fine motor skills). The muscular atrophy, a sign of lower motor neuron syndrome, was attributed to disuse. Brain MRI revealed multiple congenital abnormalities in the left cerebral hemisphere. shows gray matter heterotopia deforming the left-hand knob (black arrows); compare with the normal right-hand knob (black arrowhead). shows schizencephaly in the left precentral region (white arrows): a gray matter-lined cleft filled with cerebrospinal fluid extending from the ependyma of the lateral ventricle to the subarachnoid space of frontal region. demonstrates an absent septum pellucidum (black arrow).
These congenital malformations in the left hand knob topographically correlated with the dysfunctional right hand. However, it remained remarkable that this congenital defect led to symptoms with late onset and slow progression in this 16-year-old girl. Congenital malformations of the cerebral cortex usually present at birth or in the first decade of life (causing epileptic seizures, focal neurologic deficits or developmental decay). However, as proven in by our case, congenital defects can be associated with normal intelligence and normal neurodevelopment, and some may eventually develop symptoms later in life.


An elderly 92-year-old female noticed a palpable mass in the lower inner quadrant of her right breast for several months. The patient reported occasional palpable tenderness but no skin changes, nipple retraction, or discharge. She denied any family history of breast cancer.
A mammogram was performed and demonstrated a suspicious right breast mass (Figure ). It was followed up with ultrasound-guided core-needle breast biopsy, which further showed a large, lobulated mass corresponding to the mammographic findings suspicious for a malignant neoplasm, Breast Imaging-Reporting and Data System (BI-RADS) category 4 [].
Surgery was consulted, subsequent right breast lumpectomy and sentinel lymph node biopsy were performed. Pathology reports demonstrated malignant tumor cells with unknown etiology most likely consistent with a soft tissue mass and no lymph node involvement. She underwent a positron emission tomography (PET) scan that showed no distant metastases or axillary uptake. The patient declined any further treatment and continued to follow up with oncology with consideration for bilateral mammograms in the future.


A 76-year-old male with a history of BCC and squamous cell carcinoma presented to clinic for Mohs micrographic surgery to extirpate a biopsy-proven BCC, two weeks after initial biopsy (Figure ). Mohs surgery was performed with frozen sections, and the first stage revealed atypical basaloid cells surrounding atypical foamy cells with scalloped nuclei at the deep margin, concerning for SC (Figures -). The atypical cells were cleared on the second stage, leaving a 2.2 x 1.4 cm surgical defect size. Though SC was favored, given the equivocal pathology on frozen section (BCC with adnexal differentiation vs SC), these slides were sent to dermatopathology for tumor confirmation. A dermatopathologist re-examined the initial biopsy slide, and confirmed nodular BCC alone to be present, as seen in Figure , with morphologic features being distinct and different from the sebaceous carcinoma (Figures -). The first Mohs stage was re-embedded for permanent sectioning and immunohistochemical staining. SC at the deep margin was confirmed as seen in Figures -, as well the presence of a separate focus of BCC extending into the superficial dermis, as seen in Figure and Figure . The dermatopathologist agreed with the diagnosis of sebaceous carcinoma and favored this to be a collision lesion rather than a contiguous BCC with sebaceous differentiation. The patient continues to follow up at six-month intervals for tumor surveillance.


A 32-year-old woman, gravida 2 para 0 (two induced abortions), in vitro fertilization, group A, rhesus-positive was referred at 31+ 2 weeks gestation to our hospital due to fetal hydrops for 10 days. She had hypothyroidism during pregnancy (treated with levothyroxine). The screening test for Down’s syndrome showed low risk, and the ultrasound proved the fetus had no malformation in the second trimester. Physical examination showed 70 kg body weight and apparent edema in both legs with a peripheral blood pressure of 133/63 mmHg.
The ultrasound showed severe ascites (the deepest depth = 6.77 cm), mild edema and subcutaneous edema of the fetus (depth 0.59 cm), thickened placenta (5.8 cm), polyhydramnios (amniotic fluid index = 24.75 cm, reference value 5–18 cm), and increased peak systolic velocity of the middle cerebral artery (> 2.0 MoM, reference value < 1.5 MoM). Comprehensively, fetal anemia was considered. Maternal laboratory tests revealed anemia (100 g/L), slightly increased creatinine (91 μmol/L) and uric acid (559 μmol/L) levels, hypoproteinemia (albumin 19 g/L), and significantly increased alpha-fetoprotein (AFP, 4864.5–5005.4 ng/ml) and hemoglobin-F (HbF, 4.3%) levels. Other tests were all normal (cardiac markers, coagulation function, electrolytes) or negative (thalassemia genetic test, TORCH, HIV, syphilis, hepatitis B and C). FMH was diagnosed initially. Given that the fetus was at less than 34 weeks of gestation, dexamethasone and magnesium sulfate were used to promote lung maturation and brain protection [].
Unexpectedly, the maternal body weight increased by 6 kg (76 kg) within 2 days after admission, and she showed anasarca and started to feel chest distress, palpitation, lethargy, and oliguria (200 ml in 15 h). Preeclampsia was excluded because routine blood tests showed hemodilution. The ultrasound still showed severe ascites, edema and subcutaneous edema of the fetus, thickened placenta (5.2 cm), polyhydramnios (amniotic fluid index = 26.5 cm), increased peak systolic velocity of the middle cerebral artery (> 2.0 MoM), tricuspid regurgitation (mild), and increased cardiothoracic ratio (0.44, reference value 0.25–0.35). The fetal heart rate was normal before termination of the pregnancy. MS was diagnosed on the basis of progressive maternal edema secondary to fetal hydrops and placental edema. MS is reported to have high mortality of the fetus [, ], so emergency cesarean section was considered after a discussion involving the ICU, ultrasound team, and the neonatology, obstetrics, and anesthesiology departments. In addition, an experienced resuscitation team consisting of neonatologists, nurses and midwives was alerted for resuscitation and subsequent treatment.
The maternal clinical symptoms rapidly improved postnatally, and edema completely disappeared 4 days after cesarean section. After delivery, albumin was administered for 2 days for amelioration of hypoproteinemia, and furosemide and heparin were used for oliguria and hypercoagulability, respectively, for 5 days. Maternal AFP levels were reduced to 1278.2 ng/ml 6 days after delivery. The woman was discharged 6 days after the surgery.
A girl with a 2080-g birthweight was delivered at 31+ 4 weeks gestation. Amniotic fluid 2500 ml, clear; grossly edematous placenta (890 g, 18 × 18 × 5 cm3) (Additional file ); other labor history was normal.
After birth, the baby showed no breath, hypomyotonia and paleness. Positive pressure ventilation (PPV), endotracheal intubation, chest compressions and epinephrine infusion were performed. Notably, a bolus of 20 ml saline (within 10–15 min) was infused at 30 s after birth because hypovolemia was suspected due to severe anemia. The resuscitation process is shown in Additional file . Apgar scores were 2, 5, and 5 points at 1, 5 and 10 min, respectively. Then, the baby was transferred to the NICU under PPV via endotracheal intubation (FiO2 100%).
Spontaneous breathing of the baby appeared 17 mins after birth. Upon admission, the baby had a respiratory rate of 50–60 times/min, heart rate 144 beats/min, and peripheral blood pressure 75/48 (58) mmHg. Emergency ultrasound showed severe seroperitoneum with a maximum depth of 2.7 cm, mild hydrothorax, and no malformation of abdominal organs. To relieve respiratory distress, abdominocentesis was performed 19 min after birth, and 122 ml of light-yellow ascites was drawn out (Fig. ). The laboratory tests of ascites indicated exudates (with 85% lymphocytes).
Blood analysis and blood gas showed severe anemia, metabolic acidosis and hyperlactatemia (hemoglobin (Hb): 58 g/L, pH: 7.045, base excess: − 14.1 mmol/L, and lactate: 9.7 g/L) (Additional file ). Therefore, a rapid fluid replacement of 20 ml saline (10 mL/kg) was infused in 30 min, and a 70-ml red blood cell suspension (Type O, RhD positive) was transfused 48 mins after birth. Conventional ventilation (assist/control mode) was provided, and the initial settings were FiO2 100%, MAP 10–11 cmH2O, PIP/PEEP 20/8 cmH2O, RR 45, tidal volume 9–10 ml, and minute volume 0.4–0.5 L/min. Soon thereafter, the blood gas returned to normal gradually, the symptoms of anemia resolved, and Hb levels recovered. Approximately 4 h after birth, the ventilator settings were adjusted to FiO2 28–25%, MAP 8–9 cmH2O, PIP/PEEP 18/7 cmH2O, RR 40, tidal volume 8–9 ml, minute volume 0.3–0.4 L/min. More than 19 h after birth, the baby was extubated and supported by a humidified high-flow nasal cannula (HHFNC, FiO2 40–21%, flow 4–2 L/min) for 5 days.
To demonstrate the diagnosis of FMH, a series of etiological tests were performed in the infant (Table ). Cardiac ultrasound showed patent ductus arteriosus (2.6 mm), patent foramen ovale, tricuspid regurgitation (mild), mitral regurgitation (mild), pulmonary hypertension (46 mmHg), and the ejection fraction was normal. There was also no clinical sign of heart failure. And abdominal ultrasound proved no malformation or teratoma. All the main causes of MS or fetal hydrops were excluded [–].
We paid close attention to the neurological symptoms with regard to long-lasting severe anemia and hypoxemia both in utero and after delivery. The baby showed no clinically abnormal neurological symptoms during hospitalization. Cranial ultrasound on days 1, 2, 4 and 11 after birth revealed an increased resistance index (RI) of the middle cerebral artery but no hypoxic or ischemic changes (edema, hemorrhage, etc.) and no signs of periventricular leukomalacia (PVL). Moreover, the amplitude integrated electroencephalogram (aEEG) on the second day after birth showed that a sleep cycle appeared, a discontinuous quiet sleep period, and no seizures under video monitoring, which were all normal for a preterm infant at 31+ 5 weeks gestation. Assessment of general movements (GMs) (performed 13 days after birth) showed normal movement of the body. Both ears passed the automatic auditory brainstem response (AABR) test in the hearing screen. At 34+ 5 weeks of corrected gestation before discharge, brain magnetic resonance imaging (MRI) presented a normal structure according to gestation, and no signs of PVL or other abnormalities were noted. After 24 days of hospitalization (34+ 6 gestation), the baby was discharged with a body weight of 1810 g, body length of 40.4 cm, and head circumference of 28.5 cm. All of these values were less than the 10th percentiles, implying extrauterine growth restriction (EUGR).
After discharge, we conducted a long-term clinical follow-up for this very preterm infant. Physical development was assessed using the Fenton preterm growth chart for girls []. Although the infant had EUGR at discharge, the body weight and length gradually increased close to the 50th percentiles, and the head circumference was slower to catch-up but around the 15th percentiles at 1–5 months postmenstrual age (PMA). Regarding neurological assessments, we performed the Alberta Infant Motor Scale (AIMS) [] at 4 months PMA and the Bayley Scales of Infant Development-I (BSID-I) [] at 5 and 15 months PMA. The results showed 10th–25th percentiles for AIMS. BSID-I scores were 82 for Mental Development Index (MDI) and 83 for Psychomotor Development Index (PDI) at 5 months PMA followed by 91 for MDI and 89 for PDI at 15 months PMA. Above all, this baby only had a suspicious delay in neurodevelopmental evaluation at 5 months PMA that returned to normal at 15 months PMA.


A 26-year-old man complained of foamy urine for 3 years without hospital examination. Proteinuria was found in routine physical examinations 1 month prior, and he attended our clinic on the basis of these results. Laboratory data were as follows: urine analysis showed proteinuria (dipstick 2 +) and hematuria (3 +), 24-h uric protein quantification was 0.75 g/day (normal range, 0–0.15 g/day), and serum creatinine (Scr) was 151 μmol/L (normal range, 88–104 μmol/L). Based on abnormalities in the examination indicators, the patient was admitted to the nephrology department with an initial diagnosis of glomerulonephritis and renal insufficiency.
Further detailed consultations and examinations were carried out. The patient felt no other discomfort. His routine physical examinations showed no obvious abnormalities. He had no edema or hypertension, and his urine output was normal. During neurological examination, the patient was found to have an imperceptible tremor in his hands. A review of medical history revealed that the patient had allergic purpura 22 years prior and pneumothorax 7 years prior. The patient denied having consumed alcohol or abused drugs and denied having a history of hepatitis or family history of chronic or genetic diseases. His parents had a nonconsanguineous marriage. Laboratory examinations indicated normal white blood cell counts and hemoglobin levels. Urinalysis showed 2 + proteinuria with microhematuria (approximately 100 erythrocytes per high-power field), and his 24-h uric protein quantity fluctuated from 0.75 to 1.1 g/day. Abnormal renal function with an Scr of 150–170 μmol/L was detected. Liver function was normal, and other laboratory examinations, including serum electrolytes, thyroid function, C-reactive protein, and serum complement (C3 and C4), were also within the normal range. Additionally, immunoglobulin levels (IgG and IgM) were normal, except for mild elevation of IgA (3.73 g/L, normal range: 0.97–3.2 g/L). Serological tests were negative for anti-nuclear, anti-neutrophil cytoplasmic, anti-glomerular basement membrane, anti-hepatitis B virus, and anti-hepatitis C virus antibodies. Routine physical examination results indicated normal electrocardiogram and color Doppler ultrasound with normal kidney size and shape. Color ultrasound of the liver, gallbladder, spleen, and pancreas indicated rough echo in the liver.
Renal biopsy was performed to identify kidney disease. Analysis of renal biopsy specimens using light microscopy showed mesangial cells and matrix proliferation with glomeruli focal segmental hyperplasia and sclerosis (1/10 glomerulus; Fig. a). Epithelial cells were vacuolated and showed granular degeneration. Additionally, brush margins disappeared, the lumen dilated, and focal atrophy (atrophy area of approximately 15%) was observed in some renal tubules. Interstitial focal inflammatory cell infiltration was accompanied by fibrosis, and the walls of arterioles showed no obvious pathological changes (Fig. b). Immunofluorescence staining showed granular deposition of IgA+++ in the mesangium (Fig. c). No glomeruli were observed by electron microscopy. Silver staining showed shedding of tubule bristles and enhancement of interstitial edema (Fig. d). The pathologic diagnosis was focal hyperplastic IgA nephropathy accompanied by acute tubular interstitial injury (Lee grade III, Oxford grade M1E0S0T1).
Diagnosis of IgA nephropathy is relatively simple based on hematuria, proteinuria, and renal biopsy results; however, renal pathology may not yield a clear diagnosis. In our study, the observed pathological changes associated with IgA nephropathy did not explain the renal dysfunction in our patient. Additionally, the degree of tubular injury was not consistent with glomerular lesions. Thus, reasons other than IgA nephropathy may contribute to tubular injury. More importantly, the young patient in our study showed rough echo of the liver in our ultrasound findings. Although we repeatedly questioned the patient about his medical history, no common causes of liver damage, such as hepatitis or a history of drugs and alcohol, were reported by the patient. Furthermore, magnetic resonance imaging of the liver revealed liver atrophy and splenomegaly. The unexplained symptoms were confusing; however, the chief physician of our institution observed the mild involuntary fingertip tremors of the patient, and WD was then considered as a potential diagnosis based on this nonspecific neurological abnormality combined with the observed liver damage.
Renal biopsy was re-examined, and some subtle changes that had been overlooked on the first analysis were detected. For example, granular deposition in the cytoplasm of renal tubule epithelial cells was observed using light microscopy (Fig. a). Under electron microscopy, some renal tubular epithelial cells showed degeneration of mitochondria in the cytoplasm. The size of mitochondria varied, the inner and outer membranes were separated, and the cristae became shorter and disappeared (Fig. b). Moreover, lysosome size increased, and some round granules were deposited in the lysosome (Fig. c). Timm’s copper staining revealed some brown to black deposits in some renal tubular epithelial cells (Fig. d). Measurement of copper metabolism further confirmed the diagnosis of WD; lower levels of serum ceruloplasmin (0.02 g/L, normal range: 0.27–0.47 g/L) and increased urinary excretion of copper (260.4 μg/day, normal range: 10–60 g/day) were detected, although normal copper serum levels (12.52 μmol/L, normal range: 7.12–21.29 μmol/L) were also observed. The presence of K–F rings in the patient’s eyes, as observed by slit lamp examination, also supported the diagnosis of WD. To confirm this diagnosis, we also performed DNA sequence analysis and identified two mutations in the ATP7B gene; one was a known pathogenic mutation, whereas the other was a suspected pathogenic mutation (Table ).
Finally, the patient was diagnosed with WD. The observed kidney damage was identified as WD-associated renal injury, including renal tubulointerstitial injury and focal proliferative IgA nephropathy. The patient agreed to targeted treatment, including penicillamine 250 mg twice daily and oral zinc sulfate daily. Additionally, he was prescribed losartan to control proteinuria while monitoring renal function and blood pressure. During the 3-year follow-up, the tremor in his hands disappeared, and his 24-h uric protein level fluctuated from 0.3 to 0.5 g/day. Renal dysfunction was reversed, and Scr was maintained at approximately 110–130 μmol/L. Moreover, 24-h uric cooper dropped from 260.4 to 69 μg. The patient retained normal liver function and maintained a good quality of daily life.