Common cellular and molecular mechanisms including protein aggregation and inclusion body formation are involved in many neurodegenerative diseases. α-Synuclein is a major component of Lewy bodies in Parkinson’s disease (PD) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA). Tau is a principal component of neurofibrillary and glial tangles in tauopathies. Recently, TDP-43 was identified as a component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PD is traditionally considered a movement disorder with hallmark lesions in the brainstem pigmented nuclei. However, pathological changes occur in widespread regions of the central and peripheral nervous systems in this disease. Furthermore, primary glial involvement (“gliodegeneration”) can be observed in PD and MSA as well as in tauopathy. The present article reviews abnormal protein accumulation and inclusion body formation inside and outside the central nervous system.

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A 59-year-old woman presented with thunderclap headache. Cranial CT showed cortical subarachnoid hemorrhage (cSAH) at the right parietal lobe and cerebral angiography on day 5 revealed multiple cerebral arterial constriction, diagnosed as reversible cerebral vasoconstriction syndrome (RCVS). We could not detect vasoconstriction in MRA at the first examination on day 4, and vasoconstrictive finding appeared around Willis circle 8 days later. There was a temporal difference in a cephalalgic symptom and vasoconstrictive appearance. Clinical symptoms completely recovered and head CT, MRI/MRA findings were reversible after two months, reflecting a rather good RCVS outcome. However, we also followed up this case precisely using single photon emission computed tomography (SPECT) with easy Z-score imaging system (e-ZIS), and hypoperfusion at the locus of cSAH persisted for more than one year. This finding strongly suggests that tissue damage in the cSAH locus induced by RCVS may be subclinicaly irreversible, even though clinical symptoms and abnormalities in cranial MRI and MRA completely recover.SPECT may be a high sensitive technique to detect the irreversible lesion in RCVS.

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We describe a 34-year-old man with hypomyelination, hypogonadotropic hypogonadism, ataxia, and myopia without hypodontia. He was born to non-consanguineous parents, and had an elder brother who showed a similar phenotype. Laboratory studies demonstrated low level of LH, FSH and testosterone. MRI showed hypomyelination, atrophy of the cerebellum and the hypoplastic corpus callosum. Homozygous missensze mutation c.2350G>A (p.Gly784Ser) was found in POLR3A,which codes for the largest subunit of RNA polymerase III. Since PolIII-related leukodystrophies shows various combination of neurologic and non-neurologic features, additional reports will help to confirm the mechanism of this disease.

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We present the case of a 40-year-old woman who experienced dysarthria and, numbness in her upper extremities and posterior region of her neck. Upon admission to our hospital, neurological examination revealed rhinolalia aperta and an incomplete palatoplegia; however, muscle strength in the neck and limbs was satisfactorily preserved, tendon reflexes were normal, and pathological reflexes were not observed. Cerebrospinal fluid and electrophysiological test results were also normal. On day 3 of hospitalization, a slight backflow of fluid into the nasal cavity was observed upon deglutition, and vibration perception was also impaired in the bilateral arms. Her serum tested positive for immunoglobulin G antibodies against such gangliosides as GT1a, GQ1b, GT1b, and GD1a. Despite normal tendon reflexes, she was diagnosed with a subtype of Guillain-Barré syndrome (GBS), and was treated with intravenous immunoglobulin therapy. Subsequently, her symptoms improved. Due to the combination of oropharyngeal palsy and sensory impairment, it was more likely the GBS subtype in this patient was acute oropharyngeal palsy (AOP) rather than pharyngeal-cervical-brachial (PCB) variant; though interestingly, the patient’s sensory disturbance was limited to the posterior neck and upper extremities, which resembles the distribution of motor symptoms in PCB variant. The present case was a rare and important phenotype, demonstrating diversities of GBS variants. We also believe that GBS subtypes may represent a continuum of pathological conditions and not just one static condition. However, further studies involving serological characteristics of anti-ganglioside antibodies and clinical features for GBS are needed to clarify this possibility.

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A 42-year-old woman presented with rapid myalgia of the thigh and muscle weakness in the proximal limbs with markedly elevated serum CK. Despite positive for antibodies to anti-nuclear, anti-ds-DNA, anti-ss-DNA, anti-Sm, anti-SS-A/Ro, C-ANCA, anti-U1-RNP and anti-ribosome and slight lymphocytopenia and hypocomplementemia, there was no symptom associated with systemic lupus erythematosus (SLE). Proteinuria and hematuria were initially considered to be associated with renal damage due to myoglobinuria. Muscle MRI demonstrated high signal intensities in the rectus femoris. Muscle biopsy of the rectus femoris demonstrated a mild variation in fiber size, a few necrotic and several regenerating fibers and minimal lymphocytic infiltration in the endomysium, which suggested myopathic changes with mild necrotic and regenerating processes. Thus she was diagnosed as idiopathic myositis at first, and was treated by corticosteroid therapy. Her myalgia and CK level improved, but the proteinuria and hematuria were persistent. A renal biopsy demonstrated lupus nephritis, and SLE with myositis was confirmed. She was treated with additional tacrolimus administration, and her proteinuria and hematuria also improved. The present case suggests that patients who predominantly present with myositis accompanied by nephritis and autoantibodies should be considered as SLE with myositis.

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A 38-year old man with an 8-year history of migraine with subclinical abnormal brain lesions on MRI was admitted to our hospital. His migraine attacks followed visual disturbance or dysarthria. Brain MRI revealed old infarctions restricted to the posterior circular region. On transesophageal cardiography, an atrial septal defect (ASD) was detected, and a bubble study showed an immediate appearance of many bubbles in the left atrium via ASD without Valsalva maneuver. The bubble study on transcranial-color-flow imaging also detected micro-embolic signals at the left vertebral artery and the left middle cerebral artery without Valsalva maneuver. Since paradoxical embolism via ASD was highly suspected and Qp/Qs was more than 1.5, transcatheter closure of ASD using AMPLATZER^® Septal Occluder was performed. At a 2-year follow up, no recurrence of either migraine or infarction was found. This case indicates the relevance of right-to-left shunt to migraine with aura, as well as the usefulness of transcatheter closure of ASD using AMPLATZER^® Septal Occluder for treatment of migraine with aura.

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A 77-year-old female developed vertigo and dysarthria. Two months later, she was hospitalized with disorientation and ataxia. CSF showed increased levels of NSE, 14-3-3 protein and tau. EEG demonstrated periodic synchronous discharges (PSD). Brain MRI showed abnormal high intensity areas in the cerebral cortices, especially in the occipital lobes, putamen and caudate nucleus bilaterally, on DWI. Genetical analysis of prion protein revealed no specific mutation. She was diagnosed as having sporadic Creutzfeldt-Jakob disease (CJD). Cheyne-Stokes respiration (CSR) had been observed since an early stage, and decreased 5 months later coincident with attenuation of myoclonus and PSD. We should also pay attention to CSR in the diagnosis of CJD, although the complication is rare.

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A 63-year-old man with paroxysmal atrial fibrillation presented with aphasia (16:30) followed by right hemiplegia. The last known time that he was clinically well was 14:30. On admission (17:43), his baseline NIHSS score was 34. Head diffusion-weighted MR imaging (DWI) demonstrated large hyperintense signals throughout the left middle cerebral artery (MCA) territory. The left carotid angiogram (CAG) demonstrated occlusion of the left ICA 2 cm distal from the bifurcation. The right CAG showed a small branch laterally extending from the left anterior cerebral artery (ACA). Mechanical thrombectomy with a Merci retriever removed a large amount of thrombi after the first trial. The left ICA and MCA were recanalized to grade TICI 2b. The left hemiplegia was markedly improved, and he could walk independently. His NIHSS score was 11 at discharge. Revascularization therapy may improve a motor deficit in patients with possible penumbra of the precentral gyrus by collateral circulation from the ACA even if the ischemic lesion in the MCA territory is large on DWI.

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Neuralgic amyotrophy has been attributed to lesions in the brachial plexus. However, recent studies suggest mononeuropathy multiplex as an underlying pathology at least in a group of patients with neuralgic amyotrophy. We report a man who developed weakness of finger extensors following severe shoulder pain. Neurological examination revealed weakness in the muscles innervated by the left posterior interosseus nerve and the ulnar nerve. We diagnosed him with neuralgic amyotrophy based on the typical clinical course and the neurological and neurophysiological findings. A skeletal muscle MRI revealed abnormal high T₂ and STIR signals in the left triceps brachialis muscle, which is innervated by a proximal branch of the radial nerve, and in the muscles innervated by the posterior interosseous and ulnar nerves. The distribution of the denervated muscles suggested that our patient had combined lesions of the peripheral nerve branches rather than the brachial plexopathy. Our report highlights the potential of MRI for detecting denervated muscles in neuralgic amyotrophy.

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A 45-year-old woman was referred to our hospital by ambulance with left-sided palsy presented at dinner. Diffusion-weighted magnetic resonance imaging (DWI) showed a somewhat high intensity area in the right frontal lobe, and brain magnetic resonance angiography (MRA) revealed right middle cerebral artery (MCA) occlusion in the M1 distal segment. Although intravenous rt-PA treatment was initiated at 2 hours and 10 minutes after onset, recanalization was not achieved. The patient was diagnosed as infectious endocarditis, because highly echogenic vegetation was observed in the non-coronary cusp of the aortic valve; furthermore, Cardiobacterium hominis was incubated in blood culture, although fever was not so high and C-reactive protein (CRP) was not elevated at the time of hospitalization. It was thought that the bacteremia and infectious endocarditis had occurred due to tooth extraction about six months previously. The diagnosis of infectious endocarditis caused by the HACEK group containing C. hominis may become difficult because the fever was not so high and inflammation was not so severe.

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[in Japanese]

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[in Japanese]

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