Progressive length-dependent polyneuropathy in xeroderma pigmentosum group A.

BACKGROUND: In this study, we aimed to investigate the progression of peripheral nervous system involvement in xeroderma pigmentosum group A (XP-A). METHODS: We performed nerve conduction studies in 17 genetically confirmed XP-A patients and conducted follow-ups. Of these patients we also analyzed gray matter volume (GMV) using brain MRI and assessed the severity score of clinical and skin manifestation. RESULTS: We found significant reduction in the motor and sensory nerve action potential amplitude and mild reduction in conduction velocity. These findings were predominant in sensory nerves and the lower limbs, were observed since early childhood, and gradually deteriorated with age. CONCLUSIONS: The electrophysiological characteristics of XP-A patients are consistent with length-dependent axonal polyneuropathy and there is progressive deterioration from early childhood.

Damage to sebaceous gland and the efficacy of moisturizer after whole breast radiotherapy: a randomized controlled trial.

BACKGROUND: We conducted a randomized trial to evaluate the efficacy of heparinoid moisturization for radiation dermatitis. We report the time-course of sebum content after whole breast radiotherapy (WBRT) and the efficacy of heparinoid moisturizer. METHODS: Patients receiving adjuvant breast RT were randomly assigned into three groups; prophylaxis, post-WBRT and control groups. Patients used moisturizer on the irradiated breast from the beginning of RT in the prophylaxis group, 2 weeks post-RT in the post-WBRT group, and no moisturizer in the control group. Sebum content of the irradiated and non-irradiated breast was measured to assess sebaceous gland damage. Sebum composition was also analyzed. RESULTS: A total of 76 patients were analyzed; 30 in the post-WBRT group, 32 in the control group, 14 in the prophylaxis group. The sebum content in the irradiated breast significantly decreased after WBRT in the post-WBRT and control groups. The decrease was sustained in the control group. In the non-irradiated breast, sebum content also decreased after WBRT in the post-WBRT and control groups. After moisturizer application, sebum content by sebumeter returned to pre-RT level in the post-WBRT group, while the decrease was sustained in the control group. Sebum content measured by evaporative light scattering detector and sebumeter was similar in the control group, but the dissociation was observed after moisturizer application in the post-WBRT group. The proportion of wax esters decreased in the irradiated breast after WBRT. CONCLUSIONS: Radiotherapy significantly reduced sebum content in both irradiated and non-irradiated breast, indicating that RT caused quantifiably persistent sebaceous gland damage in irradiated sites and the surrounding tissue. Combined with the results from our previous study, heparinoid moisturizer treatment effectively prevents water loss by retaining oil contents on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000005532 . Registered 1 April 2011.

Palliative radiotherapy for breast cancer patients with skin invasion: a multi-institutional prospective observational study.

PURPOSE: To clarify the efficacy of palliative radiotherapy for the relief of symptoms due to skin invasion in patients with breast cancer. MATERIALS AND METHODS: We conducted a multi-institutional prospective observational study of patients who received palliative radiotherapy for skin invasion due to a primary lesion or chest wall recurrence. Bleeding/discharge, offensive odor, pain and QOL scores were evaluated before and 1, 3 and 6 months after radiotherapy. RESULTS: Twenty-one patients were assessed. Sixteen patients (76%) received 36 Gy in 12 fractions. The mean (±1 SD) score of bleeding/discharge was 1.90 ± 0.89 before radiotherapy, 1.50 ± 0.74 at 1 month, 0.47 ± 0.58 at 3 months, and 0.82 ± 1.04 at 6 months (P = 0.001). The mean score of offensive odor was 1.21 ± 1.38 before radiotherapy, 0.71 ± 0.92 at 1 month, 0.20 ± 0.41 at 3 months, and 0.27 ± 0.62 at 6 months (P = 0.008). The mean score of pain was 2.90 ± 1.22 before radiotherapy, 3.05 ± 1.36 at 1 month, 3.29 ± 1.10 at 3 months, and 3.31 ± 1.54 at 6 months (P = 0.431). The mean total score of QOL-ACD/QOL-ACD-B was 126.2 ± 24.5 before radiotherapy, 130.3 ± 26.3 at 1 month, 136.2 ± 26.6 at 3 months, and 126.6 ± 32.8 at 6 months (P = 0.178). CONCLUSION: Palliative radiotherapy for skin invasion in patients with breast cancer might be effective, especially for the relief of bleeding/discharge and offensive odor.

Efficacy of heparinoid moisturizer as a prophylactic agent for radiation dermatitis following radiotherapy after breast-conserving surgery: a randomized controlled trial.

BACKGROUND: The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy (WBRT) was previously reported to significantly increase skin water content (WC) and help improve skin dryness and desquamation. The prospective open-label, randomized trial included an exploratory arm to investigate the preventive efficacy of heparinoid moisturizer for acute radiation dermatitis (ARD). METHODS: Between April 2011 and April 2013, patients receiving WBRT were assigned (1:2:2) to receive either: moisturizer for prophylaxis (group P), moisturizer starting 2 weeks after WBRT for treatment (group M), and no moisturizer (group C). This paper presents the results of comparison between the exploratory arm and no moisturizer group. Skin WC was measured prior to WBRT, on the last day of WBRT, and 2 weeks, 4 weeks and 3 months following WBRT. Signs and symptoms were also assessed. RESULTS: Comparing two groups, WC values were significantly higher in group P until 4 weeks following WBRT. At 2 weeks following WBRT, mean WC values in group P and C were 38.5 ± 6.1 arbitrary units (a.u.) and 30.2 ± 7.8 a.u., respectively (P < 0.001). In group C, dryness was more severe at 2 and 4 weeks following WBRT and desquamation more severe until 3 months following WBRT. However, the erythema score showed no difference between the two groups. Regarding symptoms, group C pain scores on the last day of WBRT were significantly higher than in group P (P < 0.030). CONCLUSIONS: The preventive application of heparinoid moisturizer has the potential of reducing skin desquamation and dryness in patients receiving WBRT.

Intravenous immunoglobulin for maintenance treatment of chronic inflammatory demyelinating polyneuropathy: a multicentre, open-label, 52-week phase III trial.

OBJECTIVE: Short-term efficacy of induction therapy with intravenous immunoglobulin (Ig) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is well established. However, data of previous studies on maintenance therapy were limited up to 24-week treatment period. We aimed to investigate the efficacy and safety of longer-term intravenous Ig therapy for 52 weeks. METHODS: This study was an open-label phase 3 clinical trial conducted in 49 Japanese tertiary centres. 49 patients with CIDP who fulfilled diagnostic criteria were included. After an induction intravenous Ig therapy (0.4 g/kg/day for five consecutive days), maintenance dose intravenous Ig (1.0 g/kg) was given every 3 weeks for up to 52 weeks. The primary outcome measures were the responder rate at week 28 and relapse rate at week 52. The response and relapse were defined with the adjusted Inflammatory Neuropathy Cause and Treatment scale. RESULTS: At week 28, the responder rate was 77.6% (38/49 patients; 95% CI 63% to 88%), and the 38 responders continued the maintenance therapy. At week 52, 4 of the 38 (10.5%) had a relapse (95% CI 3% to 25%). During 52 weeks, 34 (69.4%) of the 49 enrolled patients had a maintained improvement. Adverse events were reported in 94% of the patients; two patients (66-year-old and 76-year-old men with hypertension or diabetes) developed cerebral infarction (lacunar infarct with good recovery), and the other adverse effects were mild and resolved by the end of the study period. CONCLUSIONS: Maintenance treatment with 1.0 g/kg intravenous Ig every 3 weeks is an efficacious therapy for patients with CIDP, and approximately 70% of them had a sustained remission for 52 weeks. Thrombotic complications should be carefully monitored, particularly in elderly patients with vascular risk factors. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT01824251).

Less Limb Muscle Involvement in Myositis Patients with Anti-Mitochondrial Antibodies.

Recent studies have revealed the clinical, histological, and pathophysiological characteristics in a group of inflammatory myopathies with selected autoantibodies. We retrospectively compared the clinical manifestations and histological features between 8 anti-mitochondrial (anti-M2) antibody-positive and 33 antibody-negative patients. Patients with anti-M2 antibodies have been previously reported to have delayed diagnostic confirmation and frequent cardiopulmonary complications in comparison to those without the antibodies. In our study, clinical characteristics in patients with the antibodies were as follows: lesser degree of limb muscle weakness and atrophy as well as lymphocytic infiltration in muscle biopsy specimens, and frequent paravertebral muscle atrophy. Anti-M2 antibody appeared to be a biomarker related to not only cardiopulmonary complications, but also characteristic -distributions of affected muscles.

Ultrasonographic diaphragm thickness correlates with compound muscle action potential amplitude and forced vital capacity.

INTRODUCTION: Noninvasive evaluation of respiratory function in patients with various neuromuscular disorders is important for predicting life expectancy. METHODS: We performed B-mode ultrasonography (USG) and nerve conduction studies in 37 patients (16 had amyotrophic lateral sclerosis; 11, myopathy; and 10, neuropathy) and 10 controls. USG of the diaphragm was performed in the supine position using a linear probe over the intercostal space at the anterior axillary line. Diaphragm muscle thickness was measured at end-expiration. The amplitude of diaphragm compound muscle action potentials (CMAP) was obtained by phrenic nerve stimulation with a surface electrode. Respiratory function was measured with standard pulmonary function tests including forced vital capacity (FVC). RESULTS: Diaphragm thickness was significantly correlated with FVC (r = 0.74) and CMAP amplitude (r = 0.53). CONCLUSIONS: Diaphragm USG is useful for objective evaluation of pulmonary function in neuromuscular disorders without requiring undue patient effort or cooperation.

Multiple Deep White Matter Hyperintense Lesions on Diffusion-Weighted Imaging: Early Sign of Straight Sinus Thrombosis.

Straight sinus thrombosis (SST) is a rare type of cerebral venous sinus thromboses and is extremely difficult to diagnose, especially at its acute stage. The diagnosis is often delayed in many cases of SST that leads to treatment delay and a poor prognosis. We report the case of a 67-year-old patient who had multiple deep white matter (DWM) hyperintense signals on diffusion-weighted imaging (DWI) immediately after the onset of SST. This DWM hyperintense signal on DWI was the only abnormality at the acute stage, the underlying cause of which was congestive cerebral ischemia. Taken together, DWM hyperintense signals on DWI could be a useful diagnostic imaging marker for the early detection of SST.

Randomized, prospective assessment of moisturizer efficacy for the treatment of radiation dermatitis following radiotherapy after breast-conserving surgery.

OBJECTIVE: The effect of heparinoid moisturizer use after acute skin damage for patients receiving whole-breast radiotherapy after lumpectomy is understudied. METHODS: A total of 30 patients were randomly assigned to receive heparinoid moisturizer (Group M), and 32 patients comprised the control group (Group C). Patients in Group M were instructed to apply heparinoid moisturizer from 2 weeks following whole-breast radiotherapy, and to continue to use the moisturizer until 3 months after completion of whole-breast radiotherapy. Group C patients were instructed to not apply any topical moisturizer during the study period. The relative ratio of skin water content ratio (RWCR(t) = (It /Nt)/(I0/N0)) between irradiated and non-irradiated field was calculated. Signs and symptoms were also assessed. The primary endpoint was the difference in relative ratio of skin water content ratio between 2 and 4 weeks following whole-breast radiotherapy. RESULTS: In Group C, relative ratio of skin water content ratio dropped to 0.80 ± 0.15 at 2 weeks and maintained the low level at 4 weeks following whole-breast radiotherapy. Similarly, in Group M, relative ratio of skin water content ratio dropped to 0.81 ± 0.19 at 2 weeks (prior to application), however, it returned to baseline level (1.05 ± 0.23) at 4 weeks (2 weeks after application). The arithmetic difference of relative ratio of skin water content ratio in Group M was 0.24 ± 0.23 and was significantly larger than in Group C (0.06 ± 0.15; P < 0.01). Skin dryness and desquamation were less severe in Group M. CONCLUSIONS: The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy significantly increased water content and helped improve skin dryness and desquamation compared with no use of moisturizer.

Association of the ASCO classification with the executive function subscores of the Montreal cognitive assessment in patients with postischemic stroke.

BACKGROUND: The ASCO classification can evaluate the etiology and mechanisms of ischemic stroke more comprehensively and systematically than conventional stroke classification systems such as Trial of Org 10172 in Acute Stroke Treatment (TOAST). Simultaneously, risk factors for cognitive impairment such as arterial sclerosis, leukoaraiosis, and atrial fibrillation can also be gathered and graded using the ASCO classification. METHODS: Sixty patients with postischemic stroke underwent cognitive testing, including testing by the Japanese version of the Montreal cognitive assessment (MoCA-J) and the mini-mental state examination (MMSE). Ischemic strokes were categorized and graded by the ASCO classification. In this phenotype-based classification, every patient is characterized by the A-S-C-O system (A for Atherosclerosis, S for Small vessel disease, C for Cardiac source, and O for Other cause). Each of the 4 phenotypes is graded 0, 1, 2, or 3, according to severity. The conventional TOAST classification was also applied. Correlations between individual MoCA-J/MMSE scores and the ASCO scores were assessed. RESULTS: The total score of the ASCO classification significantly correlated with the total scores of MoCA-J and MMSE. This correlation was more apparent in MoCA-J than in MMSE, because MoCA-J scores were normally distributed, whereas MMSE scores were skewed toward the higher end of the range (ceiling effect). Results for individual subtests of MoCA-J and MMSE indicated that cognitive function for visuoexecutive, calculation, abstraction, and remote recall significantly correlated with ASCO score. CONCLUSIONS: These results suggest that the ASCO phenotypic classification of stroke is useful not only for assessing the etiology of ischemic stroke but also for predicting cognitive decline after ischemic stroke.

Corrigendum: Sensory nerve action potential in patients with functional neurological disorders with sensory manifestations.

[This corrects the article DOI: 10.3389/fneur.2023.1259887.].

Efficacy and safety of mycophenolate mofetil for steroid reduction in neuromyelitis optica spectrum disorder: a prospective cohort study.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune inflammatory disease that can affect multiple generations and cause complications with long-term prednisolone treatment. This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) in preventing NMOSD relapse while reducing prednisolone dosage. The trial involved nine patients with NMOSD who received MMF along with prednisolone dose reduction. MMF was effective in achieving prednisolone dose reduction without relapse in 77.8% of patients, with a significant decrease in mean annualized relapse rate. All adverse events were mild. The findings suggest that MMF could be a viable treatment option for middle-aged and older patients who require steroid reduction.Clinical trial registration number: jRCT, jRCTs051180080. Registered February 27th, 2019-retrospectively registered, https://jrct.niph.go.jp/en-latest-detail/jRCTs051180080.

Molecular pathology of Sandhoff disease with p.Arg505Gln in HEXB: application of simulation analysis.

Sandhoff disease is a GM2 gangliosidosis caused by mutations in HEXB encoding the ß-subunit of ß-hexosaminidase A. ß-Hexosaminidase A exists as a heterodimer consisting of α- and ß-subunits, and requires a GM2 activator protein to hydrolyze GM2. To investigate the molecular pathology in an adult Sandhoff disease patient with an early disease onset, we performed mutation detection, western blot analysis and molecular simulation analysis. The patient had compound heterozygous mutations p.Arg505Gln and p.Ser341ValfsX30. Western blot analysis showed that the amount of mature form of the α- and ß-subunits was markedly decreased in the patient. We then performed docking simulation analysis of the α- and ß-subunits with p.Arg505Gln, the GM2AP/GM2 complex and ß-hexosaminidase A, and GM2 and ß-hexosaminidase A. Simulation analysis showed that p.Arg505Gln impaired each step of molecular conformation of the α- and ß-subunits heterodimer, the activator protein and GM2. The results indicated that p.Ser341ValfsX30 reduced the amount of ß-subunit, and that p.Arg505Gln hampered the maturation of α- and ß-subunits, and hindered the catalytic ability of ß-hexosaminidase A. In conclusion, various methods including simulation analysis were useful to understand the molecular pathology in Sandhoff disease.

Myositis with antimitochondrial antibodies diagnosed by rectus abdominis muscle biopsy.

INTRODUCTION: Antimitochondrial antibodies are autoantibodies detected in 90% of primary biliary cirrhosis (PBC) patients. Some PBC cases are complicated by myositis, which is difficult to confirm due to minimal histological evidence of inflammation in limb muscles. METHODS: Our aim was to determine the extent of inflammatory changes in a truncal muscle biopsy specimen from a PBC patient. RESULTS: A 48-year-old woman with a 5-year history of atrial fibrillation and chronic heart failure was evaluated for elevated serum creatine kinase level. Antimitochondrial M2 antibodies were detected, and PBC was diagnosed. A biceps brachii biopsy specimen showed mild, non-specific myogenic changes; a second biopsy was performed on the rectus abdominis muscle, which showed typical inflammatory changes. Myositis with antimitochondrial M2 antibodies was confirmed. CONCLUSIONS: In myositis patients with antimitochondrial M2 antibodies, muscles of the extremities are involved to a lesser extent. Radiological and histological examination focusing on truncal muscles, including a biopsy, is important.

Japanese structure survey of radiation oncology in 2009 with special reference to designated cancer care hospitals.

BACKGROUND: The structure of radiation oncology in designated cancer care hospitals in Japan was surveyed in terms of equipment, personnel, patient load, and geographic distribution, and compared with the structure in other radiotherapy facilities and the previous survey. METHODS: The Japanese Society for Therapeutic Radiology and Oncology surveyed the national structure of radiation oncology in 2009. The structures of 365 designated cancer care hospitals and 335 other radiotherapy facilities were compared. RESULTS: Designated cancer care hospitals accounted for 50.0% of all the radiotherapy facilities in Japan. The patterns of equipment and personnel in designated cancer care hospitals and the other radiotherapy facilities were, respectively, as follows: linear accelerators per facility: 1.4 and 1.0; dual-energy function: 78.6 and 61.3%; three-dimensional conformal radiotherapy function: 88.5 and 70.0%; intensity-modulated radiotherapy function: 51.6 and 25.3%; annual number of patients per linear accelerator: 301.3 and 185.2; Ir-192 remote-controlled after-loading systems: 31.8 and 4.2%; and average number of full-time equivalent radiation oncologists per facility: 1.8 and 0.8. Compared with the previous survey, the ownership ratio of equipment and personnel improved in both designated cancer care hospitals and the other radiotherapy facilities. Annual patient loads per full-time equivalent radiation oncologist in the designated cancer care hospitals and the other radiotherapy facilities were 225.5 and 247.6, respectively. These values exceeded the standard guidelines level of 200. CONCLUSIONS: The structure of radiation oncology in designated Japanese cancer care hospitals was more mature than that in the other radiotherapy facilities. There is still a shortage of personnel. The serious understaffing problem in radiation oncology should be corrected in the future.

Sensory nerve action potential in patients with functional neurological disorders with sensory manifestations.

Introduction: Functional neurological disorder (FND) has various clinical manifestations. Even though diagnostic criteria for FND have been proposed, FND characteristics with sensory manifestations have not been elucidated. Therefore, we aimed to investigate the association between sensory nerve action potential (SNAP) amplitudes and FND with sensory manifestations. Methods: We included 76 outpatients with FND with sensory manifestations whose nerve conduction studies were performed retrospectively. Additionally, we defined 121 patients with other neurological diseases who did not have peripheral neuropathy as disease controls. The SNAP amplitudes were compared between the two groups. We also explored the relationship between SNAP amplitudes and FND-specific clinical symptoms in patients with FND. Results: No differences were observed in SNAP amplitudes adjusted for age between patients with FND who had sensory manifestations and disease control patients. Additionally, no differences were observed between patients with FND who had and did not have FND-specific clinical symptoms. Conclusion: The SNAP amplitude in patients with FND who had sensory manifestations was equivalent to that in controls.

[Cingulate seizure as a clinical manifestation of anti-myelin oligodendrocyte glycoprotein antibody-positive cerebral cortical encephalitis of two cases].

We report two male patients who had a sensory seizure, which evolved into a focal impaired awareness tonic seizure, and after that, focal to bilateral tonic-clonic seizure. The first case, a 20-year-old man had been treated with steroids for anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive optic neuritis. His seizure started with abnormal sensation in the little finger of the left hand, which spread to the left upper and then to the left lower limb. The seizure then evolved into tonic seizures of the upper and lower limbs and he finally lost awareness. The second case, a 19-year-old man experienced floating dizziness while walking, followed by numbness and a pain-like electrical shock in the right upper limb. The right arm somatosensory seizure evolved into a right upper and lower limb tonic seizure, which spread to the bilateral limbs, and finally he lost awareness. Symptoms of both patients improved after the treatment with steroids. Both patients shared a similar high-intensity FLAIR lesion in the posterior midcingulate cortex. Both patients were diagnosed with MOG antibody-positive cerebral cortical encephalitis because of a positive titer of anti-MOG antibody in the serum. Several reports showed involvement of the cingulate gyrus in MOG antibody-positive cerebral cortical encephalitis, but only a few reported seizure semiology in detail. The semiology reported here is consistent with that of cingulate epilepsy or the findings of electrical stimulation of the cingulate cortex, namely, somatosensory (electric shock or heat sensation), motor (tonic posture), and vestibular symptoms (dizziness). Cingulate seizures should be suspected when patients show somatosensory seizures or focal tonic seizures. MOG antibody-positive cerebral cortical encephalitis should be considered as one of the differential diagnoses when the young patient shows the unique symptoms of an acute symptomatic cingulate seizure.

Nerve enlargement differs among chronic inflammatory demyelinating polyradiculoneuropathy subtypes and multifocal motor neuropathy.

Objective: We aimed to evaluate differences in ultrasonographic nerve enlargement sites among typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP, multifocal CIDP and multifocal motor neuropathy (MMN) in a Japanese population. Methods: We retrospectively reviewed medical records and selected 39 patients (14 with typical CIDP, 7 with multifocal CIDP, 4 with distal CIDP, and 14 with MMN) who underwent ultrasonography. Median and ulnar nerve cross-sectional areas (CSAs) were measured at the wrist, forearm, elbow, and upper arm. CSA ratios for each nerve were calculated as: wrist-to-forearm index (WFI) = wrist CSA/forearm CSA; elbow-to-upper arm index (EUI) = elbow CSA/upper arm CSA; and intranerve CSA variability (INCV) = maximal CSA/minimal CSA. Results: Significant differences were observed among typical CIDP, multifocal CIDP, distal CIDP, and MMN in CSA at the forearm and upper arm in the median nerves (p < 0.05). Patients with multifocal CIDP had lower WFI and EUI and higher INCV than the other groups (p < 0.05). Conclusions: Regardless of the untreated period, compared with other CIDP subtypes and MMN, multifocal CIDP showed a focal and marked nerve enlargement in the Japanese population. Significance: Differences in nerve enlargement site may be an underlying feature of multifocal CIDP.