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We report a family with adult-onset myofibrillar myopathy with BAG3 mutation who presented peroneal weakness and axonal polyneuropathy, mimicking axonal Charcot-Marie-Tooth disease. The male proband noticed difficulty in tiptoeing at age 34. At age 42, the examination showed muscle weakness and atrophy in distal lower extremities with diminished patellar and Achilles tendon reflexes. Thermal and vibration sensations were also impaired in both feet. The serum CK level was 659 U/L. On muscle imaging, predominant semitendinosus muscle atrophy coexisted with atrophies in the quadriceps, gastrocnemius and lumbar paraspinal muscles. The muscle biopsy showed myofibrillar myopathy with fiber type grouping. His 68-year-old mother also had suffered from distal leg weakness and sensory impairment since her forties. A heterozygous mutation in BAG3 (P470S) was identified in both patients. Clinical features of myofibrillar myopathy with axonal polyneuropathy were consistent with BAG3-related myopathy. Our patients showed remarkably mild presentations without cardiomyopathy, unlike the majorities of previously reported cases.

Background An early clinical differentiation between Parkinson's disease (PD) and multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) remains a challenge. The purpose of this study was to evaluate the usefulness of the combination use of midbrain-to-pontine ratio (M/P ratio) from magnetic resonance imaging (MRI) with cardiac 123I-metaiodobenzylguanidine (MIBG) uptake for differentiating PD from MSA and PSP. Methods Ninety-six parkinsonian patients (70 PD, aged 68.5 ± 9.5 years; 16 MSA, aged 67.9 ± 7.5 years; 10 PSP, aged 70.4 ± 9.4 years) who underwent MRI and cardiac MIBG scintigraphy were included in this study. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity for distinguishing PD from MSA and PSP patients. The diagnostic accuracy of these tests was also assessed among patients at the early disease stage (defined as patients with a disease duration of 3 years or less). Results The individual diagnostic sensitivity of the M/P ratio and cardiac MIBG scintigraphy was 87.1% and 67.1% in PD vs. MSA and 78.6% and 67.1% in PD vs. PSP, respectively. The diagnostic specificity of the M/P ratio and cardiac MIBG scintigraphy was 56.3% and 100% in PD vs. MSA and 70.0% and 90% in PD vs. PSP, respectively. With the optimal cutoff values, at least one positive result (either the M/P ratio or cardiac MIBG revealed abnormalities) improved sensitivity (95.7%) without decrease of specificity (56.3%) in PD vs. MSA, as well as in PD vs. PSP (100% sensitivity, 70.0% specificity). In contrast, both positive results of two tests had good specificity but low sensitivity in PD vs. MSA (60.0% sensitivity and 100% specificity) and in PD vs. PSP (47.1% sensitivity and 90% specificity). Similar trends were observed in early-stage patients. Conclusion Although M/P ratio alone was potentially useful for distinguishing PD from MSA or PSP, the combined use with cardiac MIBG scintigraphy can further improve the diagnostic accuracy of PD from MSA or PSP.

Background Neurolymphomatosis (NL) is a rare manifestation of malignant lymphoma that shows selective infiltration to the peripheral nervous system primarily or secondarily. We report a patient with secondary NL caused by germinal center B-cell (GCB)-type diffuse large B-cell lymphoma (DLBCL) who showed selective infiltration of the lumbar plexus to the spinal cord and massive nerve enlargement resulting in severe pain. Case presentation A 72-year-old female exhibited asymmetric motor and sensory impairments and pain in the lower limbs that progressed for five months. Magnetic resonance imaging (MRI) showed an enlarged lumbar plexus, which continued to the cauda equina via the L3 and L4 spinal nerves. Her symptoms gradually worsened. Ten months after the onset of symptoms, the enlarged cauda equina filled the spinal canal space, and the spinal cord was swollen. A cauda equina biopsy was performed, and she was diagnosed with GCB-type DLBCL with CD10 positivity. The primary tumor was found in a mammary cyst. The autopsy study did not show apparent infiltration, except in the nervous system. Conclusions Although there are many neurologic phenotypes of malignant lymphoma, the association between the cytological characteristics of lymphoma and the neurological phenotypes is still unclear. Several reports of CD10-positive secondary NL are available, whereas peripheral or central nervous tissue origin lymphoma cases are mostly negative for CD10. CD10 staining may be useful for distinguishing primary NL from secondary NL. NL often has a strong organotropism for peripheral nervous tissue, which makes early diagnosis challenging.

A 33-year-old man presented with slowly progressive weakness in the lower extremities over 8 years. At the age of 16 years, the elevation of serum creatine kinase level was detected. Physical examination revealed scapular winging, exaggerated lumbar lordosis and tendoachilles contracture. Gowers sign was positive and proximal dominant limb weakness was noted. Hypertrophy was observed in the upper limbs such as the biceps brachii and forearm flexor muscles. Muscle biopsy showed distinct differences in size of muscle fibers and regenerating and necrotic muscle fibers. A histological study revealed decreased calpain3 expression. Gene analysis of CAPN3 revealed two known gene mutations, leading to a diagnosis of calpainopathy (limb girdle muscular dystrophy 2A; LGMD2A). We here report our patient to discuss findings of upper limb hypertrophy, which are frequently missed compared to the lower limb, but important clinical findings.

A 68-year-old woman was referred to our hospital for progressive dizziness, gait disturbances and weight loss for 18 months. The patient was alert and showed dysphagia and a marked tendency to fall backward. Electronystagmography showed bilateral vestibular dysfunction and audiometry showed right sensorineural hearing disturbance. Cerebrospinal fluid exam showed mononuclear pleocytosis and elevated protein levels. On 18F-FDG PET/CT, abnormal uptake was observed in the mediastinal lymph nodes, from which biopsy specimens were obtained. Histological findings showed non-caseous granuloma and a diagnosis of bilateral vestibulocochlear, glossopharyngeal and vagal nerve palsies due to neurosarcoidosis was made. Steroid therapy resulted in improvement in her clinical symptoms. Neurosarcoidosis should be included in the differential diagnosis of patients showing progressive easy falling and dysphagia.

Patients with Parkinson disease (PD) often show restless legs syndrome (RLS), leg motor restlessness (LMR) and other leg restlessness (OLR) related to sensorimotor symptoms. Here, we describe 5 patients who presented with leg restlessness as an early manifestation of PD. In case 1, the patient had leg restlessness that was not LMR or RLS and preceded the onset of motor symptoms by 1 year. In case 2, LMR preceded motor symptoms by 2 years. Case 3 had unilateral RLS symptoms on the left side of the body for 33 years. Two and a half years after the spread of RLS symptoms to the right leg with increased frequency of left-sided RLS symptoms, the patient developed PD at the age of 58 years. In cases 4 and 5, RLS symptoms preceded motor symptoms by 3 months and 1 month, respectively. All patients developed Parkinsonism within 3 years (median, 1.0 year; range 0.083–2.5 years) after initial onset or exacerbation of leg restlessness. All patients had frequent leg restlessness symptoms (6–7 days per week). In our series, the preceding leg restlessness was unilateral and confined to the dominant side of the subsequent Parkinsonism, or preceding leg restlessness was bilateral but dominant on the dominant side of the subsequent Parkinsonism. Clinicians should be aware that late-onset leg restlessness (>50 years of age) including RLS, LMR, and OLR, particularly if frequent and asymmetrical, can be an early nonmotor manifestation of PD.

Rationale Pneumococcal meningitis generally develops from bacteremia and is often complicated by multiple organ infection. Patient concerns A 62-year-old man with no previous medical history developed progressive disturbance of consciousness preceded by high-grade fever and headache for a few days. Diagnosis The patient was diagnosed with pneumococcal meningitis based on meningeal irritation, polymorphonuclear cell-predominant pleocytosis of the cerebrospinal fluid (CSF) and a positive pneumococcal urinary antigen test at a different hospital. Despite the administration of meropenem and vancomycin, his consciousness worsened, and the patient was transferred to our hospital. Marked nuchal stiffness was noted. The patient showed a disturbance of consciousness, with a Glasgow Coma Scale score of E3V2M5. No significant cranial nerve palsy, motor weakness or sensory impairment was observed. CSF examination showed polynuclear cell-predominant pleocytosis of 755/μL. Transthoracic echocardiography revealed infectious endocarditis. Interventions After the detection of penicillin-susceptible Streptococcus pneumoniae, the antibiotic regimen was changed to aminobenzylpenicillin 12 g/d and ceftriaxone 4 g/d, which improved the patient's consciousness and CSF findings. However, marked neck stiffness and neck pain persisted; we performed a systemic investigation that revealed cervical vertebral osteomyelitis and aortic aneurysm. Outcomes After surgical treatment, the patient achieved complete remission of both conditions. Lessons We should consider vertebral osteomyelitis as a potential complication of meningitis when nuchal stiffness persists despite an improvement in meningitis.