[Peripheral neuropathy associated with severe glial fibrillary acidic protein (GFAP) astrocytopathy: a case report].

A 44-year-old man was admitted due to a fever. He developed unconsciousness and respiratory failure, necessitating mechanical ventilation. After the administration of methylprednisolone and intravenous immunoglobulin for suspected autoimmune encephalitis, his consciousness and respiratory state improved. However, he exhibited pronounced tetraparalysis and impaired sensation below the neck. A spinal MRI revealed swelling of the entire spinal cord, indicating myelitis. Deep tendon reflexes were diminished in all extremities, and a nerve conduction study confirmed motor-dominant axonal polyneuropathy. Subsequently, he developed a fever and headache. Brain MRI demonstrated FLAIR hyperintensities in the basal ganglia and brain stem. CSF analysis for anti-glial fibrillary acidic protein (GFAP) antibody turned out positive, leading to the diagnosis of GFAP astrocytopathy. Although the steroid re-administration improved muscle strength in his upper limbs and reduced the range of diminished sensation, severe hemiparalysis remained. Severe GFAP astrocytopathy can be involved with polyneuropathy. Early detection and therapeutic intervention for this condition may lead to a better prognosis.

Two Cases of Alice in Wonderland Syndrome with a Right Occipital Lobe Lesion Caused by Isolated Cortical Venous Thrombosis.

Alice in Wonderland syndrome (AIWS) is extremely rare, occurring more often in young individuals than in older adults. Symptoms of this syndrome typically include an altered body image, size perception, and time perception. However, the pathophysiology and lesions responsible for this syndrome remain unclear. In most cases, specific lesions cannot be identified using computed tomography or magnetic resonance imaging. Two patients with isolated cortical venous thrombosis in the right occipital area experienced transient visual symptoms of AIWS. Furthermore, a literature search indicated that AIWS with visual distortions is associated with right occipital lobe lesions, supporting the findings of our study.

Seronegative neuromyelitis optica spectrum disorder in primary familial brain calcification with PDGFB variant.

•This case indicates that the PDGFB variant is associated with PFBC as well as with NMOSD.

Bortezomib-dexamethasone versus high-dose melphalan for Japanese patients with systemic light-chain (AL) amyloidosis: a retrospective single-center study.

Bortezomib-dexamethasone (BD) and high-dose melphalan (HDM) are effective for systemic light-chain (AL) amyloidosis, but have not been compared in detail. We retrospectively investigated patients treated with BD or HDM at our center between September 2001 and June 2016. Among 234 patients, 20 were treated with BD and 30 received HDM. With the exception of age, transplant eligibility, and previous history of other chemotherapy, there were no significant differences in most background parameters between the two groups. Median age was higher (63.2 vs. 55.8, P = 0.001), number of transplant-eligible patients was lower (60.0 vs. 96.7%, P = 0.002), and number of previously treated patients was higher (35.0 vs. 0.0%, P < 0.001) in the BD group. The BD group showed trends toward lower treatment-related mortality (5.0 vs. 10.0%, P = 0.641), greater hematological response (partial response or better) (90.0 vs. 73.3%, P = 0.279), higher complete response (60 vs. 50%, P = 0.487), and similar survival with the HDM group (neither reached, P = 0.705). In conclusion, BD was as effective and safe as HDM. Notably, BD achieved this outcome among patients with poorer clinical backgrounds compared with HDM.

Polyarteritis nodosa with central nervous system involvement mimicking relapsing-remitting multiple sclerosis.

We report a patient with polyarteritis nodosa (PN) who showed frequent episodes of acute-onset central nervous system (CNS) involvement mimicking relapsing-remitting multiple sclerosis (MS) for 22 years. Long-term use of oral prednisolone successfully avoided recurrence of neurological symptoms. PN can sometimes affect the CNS, and is an important item in the differential diagnosis of neurological manifestations with lesion dissemination in time and space, as seen in MS.

Patient with adult-onset type II citrullinemia beginning 2 years after operation for duodenal malignant somatostatinoma: Indication for liver transplantation.

We report a 51-year-old female patient with adult-onset type II citrullinemia (CTLN2) who had a history of pancreatoduodenectomy for duodenal somatostatinoma with metastases to regional lymph nodes at age 49 years, paying special attention to indications for liver transplantation. At age 50 years, she developed hepatic encephalopathy with elevation of plasma ammonia and citrulline levels. A diagnosis of CTLN2 was made by DNA analysis of the SLC25A13 gene and treatment with conservative therapies was begun, including a low-carbohydrate diet and supplementation with arginine and sodium pyruvate. However, despite these treatments, frequent attacks of encephalopathy occurred with markedly elevated plasma ammonia levels. While we were apprehensive regarding the risk of recurrence of somatostatinoma due to immunosuppressive therapy after liver transplantation, the patient was in a critical condition with CTLN2 and it was decided to perform living-donor liver transplantation using a graft obtained from her son. Her postoperative clinical course was uneventful and she has had an active life without recurrence of somatostatinoma for 2 years. This is the first case of CTLN2 with somatostatinoma. As the condition of CTLN2 patients with rapidly progressive courses is often intractable by conservative therapies alone, liver transplantation should be considered even after surgery for malignant tumors in cases with neither metastasis nor recurrence.

Coadministration of tacrolimus with corticosteroid accelerates recovery in refractory patients with polymyositis/ dermatomyositis: a retrospective study.

BACKGROUND: To investigate whether or not coadministration of tacrolimus (TAC) with prednisolone (PSL) can produce a beneficial effect in the treatment of polymyositis/ dermatomyositis (PM/DM). METHODS: We reviewed medical records of 32 PM/DM patients who had been admitted to our hospital, and abstracted those who had received TAC in addition to oral PSL for treatment. The clinical usefulness of TAC in PM/DM was objectively evaluated focusing upon the manual muscle strength test (MMT) score, serum creatine kinase (CK) and tapering of PSL. RESULTS: Nine patients with PM and 6 with DM were enrolled in this study. TAC was added because of difficulty in reduction of PSL in 12 patients and recurrence with corticosteroid-induced complications in the remaining 3. Both PM and DM patients showed significant increases in the MMT score and significant decreases in serum CK 1 to 3 months after starting TAC compared with before. Skin symptoms in a clinically amyopathic DM patient also improved 1 month after starting TAC. The daily dosage of PSL could be significantly reduced in both PM and DM after starting TAC compared with before. No serious adverse events ascribable to TAC occurred in any patients. CONCLUSION: Additional use of TAC with PSL may safely promote improvement of PM/DM and also accelerate tapering of the latter.

ANCA-associated vasculitis with central retinal artery occlusion developing during treatment with methimazole.

A 63-year-old woman suddenly developed central retinal artery occlusion following a slight fever while being treated with methimazole (MMI) for hyperthyroidism. She was diagnosed to have anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on increased inflammatory reactions with positive myeloperoxidase-ANCA in the serum. Her visual acuity remained low despite immediate treatment with corticosteroids and cyclophosphamide after cessation of MMI, which may have played a role in the pathogenesis of AAV. Central retinal artery occlusion is a rare manifestation of AAV; however, it is important with regard to the possibility of serious sequelae.

First two cases of adult-onset type II citrullinemia successfully treated by deceased-donor liver transplantation in Japan.

We report the first two cases of adult-onset type II citrullinemia (CTLN2) successfully treated by liver transplantation from deceased donors in Japan. One patient was a 34-year-old female, who had suffered from depression since the age of 28 years and developed consciousness disturbance at 34 years old. The other patient was a 41-year-old man who began to experience consciousness disturbance with abnormal behavior at 37 years old. Both patients were first treated with non-surgical therapies, including low-carbohydrate diet, arginine granules and sodium pyruvate. However, their therapeutic efficacy was limited and attacks of encephalopathy occurred frequently with elevation of plasma ammonia despite treatment. While both patients and their families desired liver transplantation, no candidate donors for live-donor liver transplantation were available. Fortunately, within a relatively short period after enrollment for liver transplant from deceased donors in Japan (13 and 43 days, respectively), they underwent cadaveric liver transplantation. The clinical courses after the operation were uneventful in both cases and no attacks of hepatic encephalopathy have occurred. Although there have been no reports of good therapies for CTLN2 patients with resistance to non-surgical therapies and no live-donor candidates, our observations indicate that cadaveric liver transplantation can be a promising therapeutic option for CTLN2 patients.

Coadministration of cyclosporin a with prednisolone in acute interstitial pneumonia complicating polymyositis/dermatomyositis.

OBJECTIVE: To investigate clinical effectiveness of prednisolone (PSL) and cyclosporin A (CyA), particularly continuous intravenous administration of the latter, in patients with interstitial pneumonia (IP) associated with polymyositis/dermatomyositis (PM/DM). METHODS: We reviewed the clinical findings and therapeutic outcomes of patients with PM/DM who had received PSL and CyA (PSL + CyA, n = 21 for DM and 2 for PM) or the former alone (n = 12 for DM and 7 for PM). All patients receiving PSL + CyA had active IP. RESULTS: Fifteen of the 21 DM patients receiving PSL + CyA showed favorable therapeutic outcomes of IP (recovery group), while the remaining 6 died of respiratory failure (death group). Before treatment PaO(2) in room air and %VC were significantly lower, and the total CT score was significantly higher in the death group than in the recovery one. Continuous intravenous administration of CyA was performed in 6 patients for severe IP requiring oxygen therapy, and of these 2 showed complete recovery from it. CONCLUSIONS: Coadministration of PSL and CyA, particularly continuous intravenous infusion of the latter, from the early phase of illness may be a potent therapeutic option for PM/DM patients with decreases in PaO(2) and %VC and/or a high total CT score suggestive of a poor prognosis.

Surgical removal of amyloid-laden lymph nodes: a possible therapeutic approach in a primary systemic AL amyloidosis patient with focal lymphadenopathy.

We report a patient with primary systemic AL amyloidosis who suffered from remarkable bilateral cervical lymphadenopathy. Intensive chemotherapies, including two cycles of high-dose melphalan with autologous peripheral blood stem cell transplantation, were insufficiently effective for both the lymphadenopathy and amyloidogenic IgGλ-type M-protein in serum, but the patient showed complete haematological remission after extensive surgical removal of enlarged lymph nodes that had massive depositions of λ-type immunoglobulin light chain-derived amyloid. Lymphadenectomy may be a possible therapeutic approach with regard to both cosmetic and haematological aspects in primary systemic AL amyloidosis patients with focal lymphadenopathy.

Intestinal angina due to atherosclerosis in a 45-year-old systemic lupus erythematosus patient.

We report a patient with systemic lupus erythematosus (SLE) who developed progressive emaciation and postprandial abdominal pain with a 27-year history of corticosteroid treatment. The patient was diagnosed as having intestinal angina based on computed tomography that showed severe stenosis of the superior mesenteric artery (SMA) in addition to complete occlusion of the celiac and inferior mesenteric arteries. Histopathology of the SMA and abdominal aorta showed atherosclerosis with no vasculitis or thrombus formation. Intestinal angina should actively be considered as a possible cause of recurrent abdominal pain in SLE patients, particularly in those with a long history of disease.

Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of an amyloidogenic immunoglobulin light chain.

Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of amyloidogenic immunoglobulin light chains.

Severity and progression rate of cerebellar ataxia in 16q-linked autosomal dominant cerebellar ataxia (16q-ADCA) in the endemic Nagano Area of Japan.

16q22.1-linked autosomal dominant cerebellar ataxia (16q-ADCA) is a recently defined subtype of ADCA identified by a disease-specific C/T substitution in the 5' untranslated region of the puratrophin-1 gene. In Nagano, the central mountainous district of the main island of Japan, 16q-ADCA and spinocerebellar ataxia type 6 (SCA6) are the most and second most prevalent subtypes of ADCA, respectively. Both subtypes are classified into Harding's ADCA III, but little attention has been given to the differences in the severity and progression rate of cerebellar ataxia between 16q-ADCA and SCA6. We investigated the clinical severity and progression rate of cerebellar ataxia of 16q-ADCA patients using international cooperative ataxia rating scale and scale for the assessment and rating of ataxia and compared them with those of SCA6 patients. The age at onset was much higher in 16q-ADCA patients (60.1 +/- 9.8 years, n = 66) than in SCA6 patients (41.1 +/- 8.7 years, n = 35). Clinical features of 16q-ADCA were basically consistent with pure cerebellar ataxia, as well as in SCA6, but gaze-evoked nystagmus was observed less frequently in 16q-ADCA patients than in SCA6 patients. When compared at almost the same disease duration after onset, the severity of cerebellar ataxia was a little higher, and the progression rate seemed more rapid in 16q-ADCA patients than in SCA6 patients, but the differences were not significant.

Spinal nerve root hypertrophy on MRI: clinical significance in the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy.

OBJECTIVE: To investigate the clinical usefulness of measuring diameters of spinal nerve roots on magnetic resonance imaging (MRI) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with regard to the diagnosis and estimation of neurofunctional impairment. PATIENTS AND METHODS: Fourteen patients with CIDP (mean age, 38.9+/-19.2 years) and 10 controls were enrolled in this study. Diameters of cervical and lumbosacral spinal nerve roots were determined on the short tau inversion recovery image of MRI. Correlations between these diameters and clinical indices, including the conduction velocity of median and tibial nerves, were examined. RESULTS: Mean diameters of cervical and lumbosacral spinal nerve roots in CIDP patients were 6.0 to 6.8 mm and 7.3 to 10.4 mm, respectively. CIDP patients showed higher values of the diameter in C5 (p<0.05), C6 (p<0.05), C7 (p<0.005) and C8 (p<0.01) than controls. C7 and C8 showed significantly negative correlations between diameters of spinal nerve roots and the F-wave conduction velocity (FWCV) (p<0.05). In the lumbosacral region, L3, L4 and S1 showed significantly negative correlations between diameters of spinal nerve roots and FWCV (p<0.005, p<0.0005 and p<0.005, respectively). The latency-time difference between F- and M-waves increased with diameters of spinal nerve roots, and there were significantly positive correlations between them in L3 (p<0.05) and L4 (p<0.005). CONCLUSION: Hypertrophy of spinal nerve roots shown on MRI may be useful as a clue to the diagnosis of CIDP and also as a clinical marker suggesting impairment of peripheral nerve conduction, particularly FWCV.

Long-term follow-up of plasma cells in bone marrow and serum free light chains in primary systemic AL amyloidosis.

OBJECTIVE: Primary systemic AL amyloidosis arises from immunoglobulin light chains produced by plasma cell dyscrasia. To prospectively investigate the production of M-protein and plasma cells in bone marrow before and after chemotherapy, we performed flow cytometry and analysis of serum free light chains (FLCs). PATIENTS AND METHODS: Fifty-nine patients with primary systemic AL amyloidosis (mean age, 59.9+/-8.8 years) were enrolled in this study, and of these 31 were serially studied before and after chemotherapy. Complete hematological remission was defined as normalization of the FLC kappa/lambda ratio. RESULTS: MPC-1(-)CD45(-) (p<0.05) and MPC-1(+)CD45(-)CD49e(-) (p<0.005) were significantly higher, and MPC-1(-)-CD45(+) (p<0.05), MPC-1(+)CD45(+)CD49e(-) (p<0.0001) and MPC-1(+)CD45(+)CD49e(+) (p<0.0005) were significantly lower in the patients with AL amyloidosis than in controls. There was a significantly positive correlation between the serum predominant FLC/serum creatinine ratio and MPC-1(+)CD45(-)CD49e(-) (p<0.05). After chemotherapies, such as high-dose melphalan with autologous stem cell support, 20 of 31 patients with AL amyloidosis achieved complete hematological remission. There were no significant differences in any subtype of plasma cells before treatment between the remission and non-remission groups, but in the former group MPC-1(+)CD45(-)CD49e(-) and MPC-1(-)CD45(+) were significantly decreased and increased after chemotherapy compared with before, respectively. CONCLUSION: Abnormal plasma cells in the bone marrow, particularly the MPC-1(+)CD45(-)CD49e(-) subset, may be important as a follow-up marker before and after chemotherapy in primary systemic AL amyloidosis. These cells maintain low levels as long as no relapse occurs.

Therapeutic outcome of cyclic VAD (vincristine, doxorubicin and dexamethasone) therapy in primary systemic AL amyloidosis patients.

OBJECTIVE: Intensive chemotherapy targeting plasma cell dyscrasia has been recently employed for the treatment of primary systemic AL amyloidosis. We prospectively studied the clinical usefulness of cyclic VAD (vincristine, doxorubicin and dexamethasone) in patients with primary systemic AL amyloidosis who were ineligible for high-dose melphalan with autologous stem cell support. PATIENTS AND METHODS: Eight patients (mean age, 60.4+/-8.8 years) were treated with cyclic VAD until the disappearance of M-protein from both serum and urine. Of these, seven showed nephrotic syndrome before the start of VAD irrespective of a decrease in creatinine clearance. Serial follow-up studies after VAD evaluated hematological status and organ function. RESULTS: Four patients (50%) showed a marked decrease in abnormal plasma cells in the bone marrow and normalized kappa/lambda ratios of serum free light chain in conjunction with disappearance of M-protein after 1 to 3 courses of VAD. There were no serious adverse events, and nephrotic syndrome gradually improved with no hematological relapse in the follow-up period of 3 to 5 years. The remaining 4 patients showed worsening of congestive heart failure and/or systemic edema ascribable to dexamethasone, resulting in cessation of cyclic VAD before disappearance of M-protein. All of these patients died of multiple organ failure or required permanent hemodialysis within 1 year after the start of cyclic VAD. CONCLUSION: Cyclic VAD is a potent therapeutic option in primary systemic AL amyloidosis, but in patients with renal or cardiac dysfunction careful management for adverse events, especially body fluid retention, is necessary.

Systemic AL amyloidosis mimicking rheumatoid arthritis.

We report a patient with myeloma-associated systemic AL amyloidosis who showed chronic polyarthralgia as the main symptom. The clinical picture was similar to that of rheumatoid arthritis with regard to symmetrical swelling with tenderness in multiple joints, but inflammatory reactions were almost normal and autoantibodies were negative. He was diagnosed as having systemic AL amyloidosis based on deposition of kappa-light chain-immunoreactive amyloid in biopsied tissue and Bence Jones protein in serum and urine. Magnetic resonance imaging and bone scintigraphy suggested this disease as the cause of the polyarthralgia. Systemic AL amyloidosis may be important in the differential diagnosis of chronic polyarthralgia.