Asymptomatic Acute Cerebral Infarction in a Patient with Hemoglobin Köln.

Congenital hemoglobin disorders typically present as hemolytic anemia, but there are also numerous reports of thrombotic complications in these diseases, suggesting an associated hypercoagulative state. In hemoglobin Köln, the most common type of unstable hemoglobinopathy worldwide, there have not been many reports of such thrombotic phenomena. We herein describe the case of a patient with hemoglobin Köln demonstrating acute cerebral infarction. His father, who also had hemolytic anemia, presumably hemoglobin Köln, had a history of cerebral infarction. This case suggests that hemoglobin Köln, among other congenital hemoglobin disorders, may be a precipitating factor of thrombotic events.

Successful Treatment of Herpes Zoster Ophthalmicus Complicated by Intense Orbital Inflammation Using Laser Irradiation over the Stellate Ganglion.

A 56-year-old man presented with right-sided headache and ptosis accompanied by a facial skin rash. He was diagnosed with herpes zoster ophthalmicus (HZO). Despite acyclovir and steroid therapy, the ocular symptoms worsened. Magnetic resonance imaging (MRI) revealed severe orbital inflammation and abnormal lesions in the right trigeminal nucleus and tract. The effects of re-administration of intravenous acyclovir and steroid pulse therapy were limited. Laser irradiation of the stellate ganglion (SGL) and high-dose oral prednisolone therapy were effective. Our experience suggests the efficacy of early multimodal treatment, including SGL, in treating ocular symptoms associated with HZO.

Clinical and Genetic Features of Multiplex Families with Multiple System Atrophy and Parkinson's Disease.

While multiple system atrophy (MSA) has been considered a sporadic disease, there were previously reported multiplex families with MSA. Furthermore, several families with multiple patients with MSA and Parkinson's disease (PD) have been reported. As genetic risk factors for MSA, functionally impaired variants in COQ2 and Gaucher-disease-causing GBA variants have been reported. While it has been established that GBA variants are associated with PD, COQ2 may also be associated with PD. In 672 patients with MSA, we identified 12 multiplex families of patients with MSA and PD in first-degree relatives. We conducted a detailed analysis of the clinical presentations of these patients and genetic analyses of GBA and COQ2. In the multiplex families, a patient with MSA with predominant parkinsonism (MSA-P) was observed in nine families, while a patient with MSA cerebellar subtype (MSA-C) was observed in three families. Six families had siblings with MSA and PD, five families had a parent-offspring pair with MSA and PD, and in one family, a sibling and a parent of an MSA patient had PD. In genetic analyses of these patients, GBA variants were identified in one of the 12 MSA patients and two of the seven PD patients. Functionally impaired variants of COQ2 were identified in two of the 12 MSA patients and not identified in the seven PD patients. This study further emphasizes the occurrence of MSA and PD in first-degree relatives, raising the possibility that a common genetic basis underlies MSA and PD. Even though variants of COQ2 and GBA were identified in some patients in multiplex families with MSA and PD, it is necessary to further explore as yet unidentified genetic risk factors shared by MSA and PD.

Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy.

Autoantibodies against 3­hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ±â€¯213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ±â€¯0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ±â€¯111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ±â€¯0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ±â€¯20.8 mm/1 h; SRP, 35.7 ±â€¯26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ±â€¯36.6 mg/dL; SRP, 207.6 ±â€¯40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ±â€¯13.9 mg/dL; SRP, 46.2 ±â€¯17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM.

Botulinum toxin treatment for difficult-to-treat finger pressure ulcers caused by severe hand flexion: case report.

We report the successful treatment of two cases of difficult-to-treat pressure ulcers with botulinum toxin type A (BoNT-A). A 71-year-old male patient with Parkinson's disease presented with severe hand grip deformities of the fingers and a pressure ulcer (PU) on the right hand. He received 240U of BoNT-A into the upper limb muscles, which improved finger mobility during passive extension and resulted in resolution of the palm PU. No recurrence was noted. A 69-year-old female patient with Lewy body dementia presented with a PU on the palm side of the middle finger apex of the right hand, with exposure of the phalanx bone and dark red oedematous granulation of the tip of the finger. Severe muscle tone was noted. She received 240U of BoNT-A injected into the muscles of the upper extremities. This resulted in the disappearance of the contracture between the middle finger cusp and palm, and prompt healing of the PU. A protective finger orthosis was also used to improve hand finger grip and prevent further PUs. Although BoNT-A injection resulted in only slight improvement in the range of motion, it produced relief of pressure with consequent healing of the PU. Injection of BoNT-A into the affected muscles of the patients in this case report was effective in reducing flexor muscle tone, relief of pressure on the palm skin and healing of hand PUs.

Two Cases of Severe Type 2 Respiratory Failure Associated with Diffuse Idiopathic Skeletal Hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory process characterized by hyperostosis at tendon insertions and around joint capsules and ossification of the anterior longitudinal ligament of the spine. The flexibility of the spinal column is reduced in DISH and affects the movement of the thorax, leading to restrictive ventilatory function. In this report, we describe the first two cases of severe type 2 (hypercapnic) respiratory failure associated with DISH. Two older men presented with histories of shortness of breath. Radiography of the spine revealed DISH with coexisting ankylosis of the costovertebral joints. The patients' thoracic motion was severely restricted, reducing the mechanism of lung expansion to diaphragm contraction only. Both patients required non-invasive positive-pressure ventilation therapy to cope with their conditions. Our report sheds light on the risk of potentially life-threatening respiratory manifestations of DISH among older adults.

Spontaneous Intracranial Hypotension with a Reversible Splenial Lesion after Swimming.

Spontaneous intracranial hypotension (SIH) is an important cause of headache mainly associated with spinal cerebrospinal fluid leakage. We herein report the case of a 51-year-old man who developed SIH after swimming. Brain magnetic resonance imaging (MRI) showed a transient high-intensity lesion in the splenium of the corpus callosum (SCC), in addition to bilateral subdural hematomas (SDH) and pseudo-subarachnoid hemorrhage on brain computed tomography. The splenial lesion disappeared and SDH improved after an epidural blood patch. This case emphasizes that transient SCC lesions could coexist with SIH and that SIH should be considered in the differential diagnosis of SCC lesions.

A central nervous system metastasis of melanoma with stroke-like onset of left-lower quadrantanopsia.

"Stroke mimics" mean diseases presenting with acute neurological impairments that are taken for stroke. Discriminating them is crucial to avoid improper treatment or delayed correct treatment. We describe a 48-year-old woman presenting with a sudden onset of scintillating scotoma and left-lower quadrantanopsia. Hyperacute cerebral infarction was suspected. However, brain magnetic resonance imaging (MRI) revealed a mass at the cortico-medullary junction in the right occipital lobe. We diagnosed her as metastatic melanoma. We suspected that neurological deficits can be attributed to seizure, and therefore introduced levetiracetam. She showed neurological improvement immediately. Our case demonstrated the importance of considering brain tumor as a differential diagnosis in patients presenting with acute-onset neurological deficits. In addition to appropriate treatment of tumor, the use of newer antiepileptic drugs resulted in good neurological prognosis in metastatic brain tumors.

Corticobasal degeneration with deep white matter lesion diagnosed by brain biopsy.

Corticobasal degeneration (CBD) is a rare progressive neurodegenerative disorder characterized by asymmetric presentation of cerebral cortex signs, cortical sensory disturbance and extrapyramidal signs. Herein, we report a case of a 66-year-old Japanese woman who presented with apraxia of the right hand. She subsequently developed postural instability and cognitive impairments that rapidly worsened. One and a half years later, the patient was wheelchair-bound and severely demented. Brain magnetic resonance imaging revealed left dominant atrophy of the frontoparietal lobe. There was a hyperintense lesion in the deep white matter expanding toward the subcortical area on fluid-attenuated inversion recovery (FLAIR) images. In order to rule out the possibility of an intracranial tumor such as an astrocytoma or malignant lymphoma, we performed a brain biopsy of the left frontal middle gyrus. The patient became bedridden and showed akinetic mutism 1 year after biopsy. Pathological examination revealed a large amount of 4-repeat tau-immunoreactive neuropil threads scattered predominantly in the corticomedullary junction and tau-immunoreactive structures, consistent with CBD. Immunostaining for p53 showed no positive cells, and there were very few Ki-67-positive cells. On immunoblots of sarkosyl-insoluble brain extracts, a major doublet of 64 and 68 kDa full-length tau with two closely related fragments of approximately 37 kDa were detected. Based on these results, the patient was pathologically diagnosed as having CBD, excluding the possibility of tumor. Taken together with previous similar case reports, our findings indicate that a deep white matter hyperintense lesion on FLAIR images may be a useful clue to CBD, predicting rapid clinical progression with severe dementia based on severe white matter degeneration with a large amount of tau accumulation on pathological examination.

Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease.

Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.

Tumefactive multiple sclerosis which initially presented with brainstem encephalitis with a long-term follow-up.

Tumefactive demyelinating lesions (TDLs) are rare in multiple sclerosis (MS). We herein report a case of tumefactive MS which initially presented with brainstem encephalitis with a long-term follow-up. The patient had experienced relapse mostly in the brainstem in the first twenty years, and then in the periventricular white matter afterwards. The patient responded well to steroid treatment recovered without sequalae. However, immunodeficiency due to the long-term use of oral prednisolone made aggressive therapy during the relapse impossible, so recovery after steroid therapy is incomplete. Our case is different from classical MS in clinical course and response to treatment. Our report offers rare information on long-term outcome of tumefactive MS.

Inflammatory myopathy with myasthenia gravis: Thymoma association and polymyositis pathology.

Objective: To provide evidence that idiopathic inflammatory myopathy (IM) with myasthenia gravis (MG) frequently shows thymoma association and polymyositis (PM) pathology and shares clinicopathologic characteristics with IM induced by immune checkpoint inhibitors (ICIs). Methods: We analyzed the clinicopathologic features of 10 patients with idiopathic IM and MG identified in 970 consecutive patients with biopsy-proven IM. Results: Seven patients (70%) had thymoma. IM and MG were diagnosed with more than 5-year time difference in 6 thymomatous patients and within 1 year in 1 thymomatous and 3 nonthymomatous patients. Seven thymomatous patients showed rhabdomyolysis-like features with respiratory failure (4/7), dropped head (3/7), cardiac involvement (2/7), and positive anti-acetylcholine receptor (anti-AChR) and anti-titin antibodies (7/7 and 4/6, respectively) but rarely showed ocular symptoms (2/7) or decremental repetitive nerve stimulation (RNS) responses (1/7) at IM diagnosis. Three nonthymomatous patients showed acute cardiorespiratory failure with rhabdomyolysis-like features (1/3), positive anti-AChR and anti-titin antibodies (3/2 and 2/2, respectively), and fluctuating weakness of the skeletal muscle without ocular symptoms (3/3). Muscle pathology showed a PM pathology with infiltration of CD8-positive CD45RA-negative T-lymphocytes (9/9), scattered endomysial programmed cell death 1 (PD-1)-positive cells (9/9), and overexpression of programmed cell death ligand 1 (PD-L1) on the sarcolemma of muscle fibers around the infiltrating PD-1-positive cells (7/9). Conclusion: Rhabdomyolysis-like features, positive anti-AChR antibody without decremental RNS responses, and PD-L1 overexpression are possible characteristics shared by ICI-induced IM. Frequent thymoma association in patients with idiopathic IM and MG may suggest thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway.

[Anti-Hu antibody positive sensory neuronopathy causing painful legs and moving toes (PLMT) in a 75-year-old female with small cell lung cancer (SCLC)].

The case is a 75-year-old female. She had dysesthesia in the distal extremities and truncal ataxia, and they had progressed in two months. Neurological examination revealed the findings of segmental dysesthesia in the distal extremities, impaired deep sensations in the trunk and four limbs, and painful legs and moving toes (PLMT). After workup, she was diagnosed with small cell lung cancer and her blood sample was positive for anti-Hu antibody. We concluded that her neurological symptoms were attributable to sensory neuronopathy associated with paraneoplastic syndrome. No cases with PLMT caused by paraneoplastic syndrome have been reported so far. She had chemotherapy to lung cancer and Duloxetine without improvement of PLMT. On the other hand, intravenous immunoglobulin treatment improved lightening pain in the toes without improvement of moving toes.

Severe pleuritis and pericarditis associated with very-late-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multisystem disorder, which occurs mostly in young women. However, late-onset SLE does exist and sometimes presents with an atypical, diversified course. We describe an 85-year-old woman who was admitted to our hospital for lower extremity edema and hand grip weakness. Chest computed tomography scan 4 days after admission demonstrated rapid accumulation of pleural and pericardial effusions, which did not exist on admission. She was diagnosed with pleuritis and pericarditis associated with very-late-onset SLE. Methylprednisolone pulse therapy resulted in a drastic improvement in serositis. Our case exemplifies the fact that patients with late-onset SLE sometimes follow an atypical course, which makes the clinical diagnosis difficult.

Paraspinal muscle involvement in herpes zoster-induced abdominal wall pseudohernia revealed by electrophysiological and radiological studies.

Segmental zoster paresis is an uncommon complication of herpes zoster, and abdominal wall pseudohernia is rare. Previous reports have emphasized the involvement of anterior rami of spinal nerves, while the involvement of posterior rami has been less frequently reported. We aimed to elucidate the involvement of posterior rami of spinal nerves in abdominal wall pseudohernia. Four patients with a diagnosis of abdominal wall pseudohernia underwent needle electromyography (nEMG) and magnetic resonance imaging (MRI). In three patients, nEMG of affected paraspinal muscles showed denervation potentials, and MRI showed hyperintensity of these muscles on short T1 inversion recovery imaging. These results suggested involvement of paraspinal muscles, and indicated that posterior rami of spinal nerves are also often affected in abdominal wall pseudohernia. MRI as well as nEMG could be useful for evaluating paraspinal muscle involvement and for the diagnosis.