Thymoma-associated anti-LGI1 encephalitis and myasthenia gravis: A unique combination with autoantibodies.

We report a 77-year-old woman with a thymoma, anti-LGI1antibody associated encephalitis (LGI1 encephalitis), and MG accompanied by positive anti-acetylcholine receptor antibodies (AchR Ab) and anti-titin antibodies (titin Ab). She was treated with thymomectomy followed by immunosuppressive therapy, which resulted in immediate amelioration of motor weakness and gradual improvement of cognitive impairment over the next two years. LGI1 Ab were positive at two months after thymomectomy, followed by negative conversion demonstrated on 1 year examination. The AchR Ab level had gradually decreased but titin Ab was positive on re-examination after two years, although the cognition and motor impairment symptoms had been alleviated. In patients with suspected autoimmune encephalitis, the detection of several autoantibodies including LGI1 and thymomas provides useful information for making an accurate diagnosis.

Pathological findings in a patient with non-dystrophic myotonia with a mutation of the SCN4A gene; a case report.

BACKGROUND: Non-dystrophic myotonias (NDMs) are skeletal muscle disorders involving myotonia distinct from myotonic dystrophy. It has been reported that the muscle pathology is usually normal or comprises mild myopathic changes in NDMs. We describe various pathological findings mimicking those of myotonic dystrophy (DM) in biopsied muscle specimens from a patient with NDMs with a long disease duration. CASE PRESENTATION: A 66-year-old Japanease man presented eye closure myotonia, percussion myotonia and grip myotonia together with the warm-up phenomenon and cold aggravation from early childhood. On genetic analysis, a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.L689F), with no mutation of the CLCN1, DMPK, or ZNF9/CNBP gene, was detected. He was diagnosed as having NDMs. A biopsy of the biceps brachii muscle showed increasing fiber size variation, internal nuclei, chained nuclei, necrotic fibers, fiber splitting, endomysial fibrosis, pyknotic nuclear clumps and disorganized intermyofibrillar networks. Sarcoplasmic masses, tubular aggregates and ragged-red fibers were absent. CONCLUSION: It is noteworthy that the present study revealed various pathological findings resembling those seen in DM, although the pathology is usually normal or mild in NDMs. The pathological similarities may be due to muscular modification with long-standing myotonia or excessive muscle contraction based on abnormal channel activity.

Non-convulsive status epilepticus associated with neuronal intranuclear inclusion disease: A case report and literature review.

We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. Brain magnetic resonance imaging showed mild cerebral atrophy and linear hyperintensities at the corticomedullary junction on diffusion-weighted images. This patient developed nonconvulsive status epilepticus with generalized periodic discharges on electroencephalography after recurrent symptoms of paroxysmal nausea and slowly progressive cognitive decline. There have been no previous reports of NIID with nonconvulsive status epilepticus to our knowledge. Since adult patients with NIID display a wide variety of clinical manifestations, skin biopsy should be considered in patients who have leukoencephalopathy of unknown origin.

Multiple pseudofractures due to Fanconi's syndrome associated with Wilson's disease.

We report a 40-year-old man who presented with multiple bone pseudofractures after about 20 years from the onset of Wilson's disease (WD). At age 36, he first noticed pain in his left shoulder. At age 39, he had multiple chest pain. On neurologic examinations, dysarthria and dysphagia due to pseudobulbar palsy, rigidity and tremor on right upper lim were observed. WD was confirmed because of low levels of plasma cupper and ceruloplasmin in addition to ATP7B gene mutation. The chest X-ray revealed multiple fractures of the several ribs. We diagnosed osteomalacia due to Fanconi's syndrome because of hypophosphatemia and the impairment of renal tubules for WD. After administration of vitamin D, there happened no new bone pseudofractures. Although bone pseudofractures accompanied by Wilson's disease generally happen in childhood, we should be aware of this symptom even in adulthood.

[A Case of Acute Limbic Encephalitis with Sjögren's Syndrome].

A 52-year-old woman developed abnormal behavior and disturbance of consciousness subsequent to several days with a cold. On admission, she was very confused, with incoherent speech, and an inability to recognize family faces. Diffusion weighted MRI showed high intensity signal change in the bilateral medial temporal lobes, including the hippocampus. Cerebrospinal fluid examination was normal. Tests including various viral antibody titers provided no evidence of infection. Several neuronal antibodies including anti-VGKC and -NMDA receptor antibody were absent. Evidence of malignancy was not apparent. She was diagnosed with acute limbic encephalitis complicated by Sjögren's syndrome (SjS), due to the fact that she had a past history of SjS, elevation of anti-SS-A antibody, pleuritis and pericarditis. Her symptoms gradually improved after administration of steroids including pulse therapy; however, her amnesia remained for a long time. In diagnosing acute limbic encephalitis, we should consider SjS as an underlying disease, even though it is rare.

Opsoclonus-myoclonus syndrome associated with multiple system atrophy.

Opsoclonus-myoclonus syndrome (OMS) is well known as a paraneoplastic syndrome or as a parainfectious neurologic complication. However, OMS associated with a neurodegenerative disorder has not been described previously. A 48-year-old woman had been diagnosed as multiple system atrophy-parkinsonian type (MSA-P) based on the findings of dopamine non-responsive parkinsonism with autonomic failure and typical findings on magnetic resonance imaging 5 years ago. She exhibited recurrent asynchronous and arrhythmic myoclonic movements of the upper limbs and abdomen with a very short duration, and involuntary eye movements, which were repetitive, rapid, random, multidirectional, conjugate saccades of irregular amplitude and frequency at rest. Based on hematological and radiological findings, the diagnosis was advanced MSA-P associated with OMS. As far as we are aware, there have not been any previous reports of such a case.

[Cheyne-Stokes respiration appeared in an early stage of the disease in a patient with Creutzfeldt-Jakob disease].

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.

Familial amyloidotic polyneuropathy and transthyretin.

There has been much progress in our understanding of transthyretin (TTR)-related amyloidosis including familial amyloidotic polyneuropathy (FAP), senile systemic amyloidosis and its related disorders from many clinical and experimental aspects. FAP is an inherited severe systemic amyloidosis caused by mutated TTR, and characterized by amyloid deposition mainly in the peripheral nervous system and the heart. Liver transplantation is the only available treatment for the disease. FAP is now recognized not to be a rare disease, and to have many variations based on genetical and biochemical variations of TTR. This chapter covers the recent advances in the clinical and pathological aspects of, and therapeutic approaches to FAP, and the trend as to the molecular pathogenesis of TTR.

[Atypical distribution of muscular atrophy in a 29-year-old man with polymyositis and anti-SRP antibodies].

A 29-year-old man developed muscle weakness in the neck at age 27. An increasing serum creatine kinase (CK) activity was detected. The first examination at our hospital revealed severe muscular atrophy at the front of the neck. Subsequently, muscular atrophy and weakness developed in the shoulders and upper extremities with an increasing serum CK level, which reached 9,159 IU/l. Needle electromyography (EMG) was not able to reveal typical myopathic change represented low-amplitude motor unit potentials (MUPs) in the proximal parts of the upper and lower extremities at the first examination, but in the course of the disease, the MUPs amplitude decrease in the same muscles. Serum examination gave a positive result for anti-signal recognition particle (SRP) antibodies. A biopsy of the deltoid muscle revealed necrotizing myopathy including small angular fiber-like atrophy without inflammatory cell infiltration or fibrotic proliferation. He was treated with prednisolone and tacrolimus with the diagnosis of polymyositis. The characteristic feature in this patient is that muscular atrophy and weakness were mainly observed in the neck. Moreover, the neurogenic changes on EMG in the early stage are also observed on atypical. Polymyositis with anti-SRP antibodies has the distinctive feature of typical polymyositis with cellular infiltration clinically and pathologically. In this respect, this case has striking and suggestive features of polymyositis with anti-SRP antibodies.

[Clinical features of neuroferritinopathy].

Neuroferritinopathy is an autosomal dominant basal ganglia disease with iron accumulation caused by a mutation of the gene encoding ferritin light polypeptide (FTL). Six pathogenic mutations in the FTL gene have so far been reported. One such mutation was found in a Japanese family, thus suggesting that a new mutation in the FTL gene can therefore occur anywhere in the world. The typical clinical features of neuroferritinopathy are dystonia (especially orofacial dystonia related to speech and leading to dysarthrophonia) and involuntary movement, but such features vary greatly among the affected individuals. The findings of excess iron storage and cystic changes involving the globus pallidus and the putamen on brain MRI. and low serum ferritin levels are characteristic in neuroferritinopathy. Brain histochemistry shows abnormal aggregates of ferritin and iron throughout the central nervous system. Iron atoms are stored in the central cavity of the ferritin polymer and the E-helices of ferritin play an important role in maintaining the central cavity. A mutation in exon 4 of the FTL gene is known to alter the structure of E-helices, thereby leading to the release of free iron and excessive oxidative stress. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial, however before the nset of clinical symptoms, such a treatment strategy may still have some benefit. Neuroferritinopathy should therefore be considered in all patients presenting with basal ganglia disorders of unknown origin. These characteristic MRI findings may help to differentiate neuroferritinopathy from other diseases showing similar clinical features.

Clinical and histopathological features of progressive-type familial amyloidotic polyneuropathy with TTR Lys54.

The purpose of this study was to evaluate the clinical and pathological features in patients with progressive-type familial amyloidotic polyneuropathy (FAP) using autopsy and biopsy specimens. A proband is a 33-year-old man with FAP type I who developed motor, sensory and autonomic impairments with neuropathy, heart failure, and anorexia. Genetic findings of transthyretin (TTR) revealed G to A transition in codon 54 causing a rare mutation of TTR Lys54. He died of pneumonia and severe cardiac failure 4 years after onset. Autopsy showed heavy amyloid deposition in the heart, peripheral nerves, thyroid, skin, fat tissue, prostate and testis, moderate in the sympathetic nerve trunk, vagal nerve, celiac plexus, pelvic plexus, bladder, gastrointestinal tract, tongue, pancreas, lung, pituitary, blood vessel, gall bladder, adrenals and muscles, and free in the central nervous system, liver, kidney and spleen. Sural nerve biopsy in a sibling confirmed TTR amyloidosis immunohistochemically. Electronmicroscopic findings of amyloid fibrils were similar to that of FAP Met30. Immunoelectronmicroscopic findings indicated the relationship between amyloid fibrils or non-fibrillar structure and collagen fibers. The distribution of amyloid deposition, heavy in the heart and lacking in the kidney, is a characteristic feature and reflected severity of FAP with TTR Lys54.

Intramedullary tuberculoma with syringomyelia.

Intramedullary tuberculoma with syringomyelia is rare. We treated a woman with back pain and weakness of the left leg that had slowly progressed for more than 30 years. Radiologic evaluation demonstrated a crescent-shaped calcification at the level of the C6 vertebra, and syringomyelia from C7 to T9. Laminectomy and syringosubdural shunt placement were performed, and a tuberculoma was removed. Back pain resolved after the operation, and mobility was facilitated. We recommend surgery for intrathecal tuberculoma with syringomyelia even when the course has been prolonged with no active tuberculous lesion.