Altered Functional Connectivity during Mild Transient Respiratory Impairment Induced by a Resistive Load.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without altering transcutaneous oxygen saturation. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptual area (postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores. These findings may provide new insights into the visual networks that contribute to mild respiratory impairments.

[A case of very long chain acyl-CoA dehydrogenase deficiency diagnosed due to a trigger of hyperemesis gravidarum during pregnancy].

A 25-year-old Japanese woman with a history of repeated episodes of rhabdomyolysis since the age of 12 presented with rhabdomyolysis caused by hyperemesis gravidarum. Blood tests showed an elevated serum CK level (11,755 |IU/l; normal: 30-180 |IU/l). Carnitine fractionation analysis revealed low levels of total carnitine (18.3 |µmol/l; normal: 45-91 |µmol/l), free carnitine (13.1 |µmol/l; normal: 36-74 |µmol/l), and acylcarnitine (5.2 |µmol/l; normal: 6-23 |µmol/l). Tandem mass spectrometry showed high levels of C14:1 acylcarnitine (0.84 |nmol/ml: normal: <0.4 |nmol/ml) and a high C14:1/C2 ratio of 0.253 (normal: <0.013), indicating a potential diagnosis of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. In Japan, neonatal mass screening is performed to detect congenital metabolic diseases. With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. However, it is important to note that mass screening cannot detect all cases of this disease. For patients with recurrent rhabdomyolysis, it is essential to consider congenital diseases, including fatty acid metabolism disorders, as a potential diagnosis.

Association of Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease with Coronavirus Disease 2019 Vaccination and Infection: A Case Report of Cortical Encephalitis and Transverse Myelitis Relapse.

We herein report a case of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) that occurred following coronavirus disease 2019 (COVID-19) vaccination and its subsequent relapse after COVID-19 infection. A 34-year-old woman developed cortical encephalitis in the right temporoparietal lobe one week after receiving the mRNA-1273 vaccine. The cerebrospinal fluid was positive for anti-MOG antibody. Her symptoms gradually improved after three courses of intravenous methylprednisolone therapy. Six months later, she experienced a relapse of transverse myelitis following COVID-19 infection. Despite treatment with plasma exchange, the patient remained paralyzed in both lower limbs. We herein review the relationship between MOGAD and COVID-19 vaccination/infection.

Hereditary Neuralgic Amyotrophy with a Lesion Distal to the Brachial Plexus on Magnetic Resonance Imaging.

A 35-year-old woman first experienced left upper limb weakness at 17 years old, after which it repeatedly recurred and then remitted. She was diagnosed with carpal tunnel syndrome with median nerve hyperintensity by magnetic resonance imaging (MRI). Surgical treatment was ineffective. We suspected hereditary neuralgic amyotrophy because of enlargement distal to the brachial plexus on MRI and administered steroid therapy, after which the weakness improved. Genetic testing revealed a point mutation in SEPT9. Because lesions outside the brachial plexus can be seen in hereditary neuralgic amyotrophy, the diagnosis should be based on typical characteristics and the family history.

[Chronic progressive external ophthalmoplegia that could not be diagnosed by biceps muscle biopsy, but was genetically diagnosed by extraocular muscle biopsy].

A 48-year-old Japanese male experienced slowly progressive diplopia. He had no family history and was negative for the edrophonium chloride test. Blood analysis showed elevated lactic acid and pyruvic acid levels, suggesting mitochondrial disease. A muscle biopsy from the biceps brachii was performed, but no pathological or genetical mitochondrial abnormalities were detected. Subsequently, he underwent muscle plication for diplopia in which the right inferior rectus muscle was biopsied. Genetic examination of genomic DNA extracted from the extraocular muscle tissue revealed multiple mitochondrial gene deletions, with a heteroplasmy rate of approximately 35%, resulting in the diagnosis of chronic progressive external ophthalmoplegia. In mitochondrial diseases, the tissue distribution of mitochondria with disease-associated variants in mtDNA should be noted, and it is important to select the affected muscle when performing a biopsy for an accurate diagnosis.

Anti-glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus initially presenting with one-sided stiff face: A case report.

Background: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome, a rare cerebrospinal disease that causes brainstem symptoms, myoclonus, muscle rigidity, and hyperekplexia. Case presentation: A 71-year-old man experienced left-sided stiff face, and was subsequently admitted to our hospital because of the appearance of left-dominant lower limb myoclonus. Muscle rigidity followed 3 days later. Magnetic resonance imaging revealed no abnormality. An electrophysiological examination showed a toughness of the antagonistic muscle following evocation of the Achilles tendon reflex, and a tonic phenomenon affecting the left facial muscles during the blink reflex. The patient's serum was positive for anti-glycine receptor (anti-GlyR) antibody, suggesting PERM. The patient was administered steroids, immunoglobulin therapy, and immunosuppressive drugs. He gradually improved after these therapies and became able to walk using a walker. Conclusions: We conclude that this was a rare case of anti-GlyR antibody-positive PERM with unilateral brainstem symptoms, myoclonus, and muscle rigidity.

[A case of localized fasciitis with ulcerative colitis].

A 36-year-old man with ulcerative colitis presented with bloody stools at the beginning of October 2020. His condition had been stable without treatment since diagnosis 4 years prior. He was administered 4,000 mg of salazosulfapyridine orally and the bloody stools resolved. Fifteen days after treatment, he was admitted to our hospital with swelling and pain in his right lower leg. Laboratory results revealed an elevated erythrocyte sedimentation rate (43 mm/hr) and mildly elevated C-reactive protein levels (4.08 mg/dl). His D-dimer level was also elevated at 7.6 µg/ml. MRI using fat saturated T2-weighted imaging demonstrated marked hyperintensity in the fascia of the lower leg flexor and blood vessels of interstitial. In gadolinium-enhanced T1-weighted images, the deep veins were found to be dilated and the vein walls and their surrounding areas strongly contrasted, suggestive of localized fasciitis. No abnormalities were found on biopsy of his right gastrocnemius muscle on the 5th day after admission. Two days after the muscle biopsy, the patient began experiencing swelling and pain in his left lower leg. The high intensity lesions in his right leg were reduced on MRI performed the same day, but that of the fascia between the left gastrocnemius and soleus muscles was noted. We administered 60 mg (1.0 mg/kg/day) of prednisolone orally on day 9 and the pain and swelling in both legs promptly resolved. The prednisolone was tapered to 5 mg/day and as of the time of writing, resolution of pain and swelling has been maintained. Gastrocnemius myalgia syndrome, which causes pain and localized fasciitis, is often reported as a complication of Crohn's disease but is rare in conjunction with ulcerative colitis. It is important that clinicians are aware of this syndrome so it can be recognized early and successfully treated.

Comprehensive Research on Past and Future Therapeutic Strategies Devoted to Treatment of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly debilitating fatal neurodegenerative disorder, causing muscle atrophy and weakness, which leads to paralysis and eventual death. ALS has a multifaceted nature affected by many pathological mechanisms, including oxidative stress (also via protein aggregation), mitochondrial dysfunction, glutamate-induced excitotoxicity, apoptosis, neuroinflammation, axonal degeneration, skeletal muscle deterioration and viruses. This complexity is a major obstacle in defeating ALS. At present, riluzole and edaravone are the only drugs that have passed clinical trials for the treatment of ALS, notwithstanding that they showed modest benefits in a limited population of ALS. A dextromethorphan hydrobromide and quinidine sulfate combination was also approved to treat pseudobulbar affect (PBA) in the course of ALS. Globally, there is a struggle to prevent or alleviate the symptoms of this neurodegenerative disease, including implementation of antisense oligonucleotides (ASOs), induced pluripotent stem cells (iPSCs), CRISPR-9/Cas technique, non-invasive brain stimulation (NIBS) or ALS-on-a-chip technology. Additionally, researchers have synthesized and screened new compounds to be effective in ALS beyond the drug repurposing strategy. Despite all these efforts, ALS treatment is largely limited to palliative care, and there is a strong need for new therapeutics to be developed. This review focuses on and discusses which therapeutic strategies have been followed so far and what can be done in the future for the treatment of ALS.

Cerebral Tuberculoma with Mild Posterior Cervical Pain as the Main Symptom Despite Extensive Brain Lesions.

A 59-year-old woman with a diabetes history experienced mild neck pain. A neurological examination revealed only mild neck stiffness. Magnetic resonance imaging showed extensive T2-weighted high-intensity lesions with patchy gadolinium enhancement mainly involving the white matter in the right parietal lobe. A cerebrospinal fluid analysis revealed increased protein levels and pleocytosis. While QuantiFERON-TB Gold was positive, computed tomography (CT) and fluorodeoxyglucose on positron emission tomography-CT of the whole body showed no abnormal accumulation, suggesting tuberculosis. A brain biopsy revealed cerebral tuberculoma. As cerebral tuberculoma can show minimal neurological symptoms despite extensive lesions, a cautious examination and early treatment are required to prevent a devastating prognosis.

Therapeutic Experience of Progressive Multifocal Leukoencephalopathy Development during Ofatumumab Therapy for Chronic Lymphocytic Leukemia.

A 79-year-old man experienced cognitive impairment and visual field defects during ofatumumab therapy for chronic lymphocytic leukemia refractory to combination chemotherapy. Magnetic resonance imaging revealed T1-weighted low-intensity and T2-weighted high-intensity lesions with patchy gadolinium enhancement in the subcortical white matter. A diagnosis of progressive multifocal leukoencephalopathy was made after the detection of John Cunningham virus (JCV) DNA in his cerebrospinal fluid (CSF). Following plasma exchange and the administration of mirtazapine and mefloquine, the JCV DNA levels in the CSF decreased. However, the patient died 55 days after treatment was initiated. Ofatumumab treatment appears to be associated with the development of progressive multifocal leukoencephalopathy.

A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene.

Spastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a "likely pathogenic" variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.

[A case of brain tuberculoma resembling a malignant tumor].

A 35-year-old Sudanese man experienced bitter tastes on the right side of his tongue from January 2012. He was admitted to our hospital in March 2012 because of the appearance of distress, right facial palsy, nausea, and dizziness from late February 2012. A neurological examination revealed Bruns nystagmus, which increased on rightward gaze, as well as total hypoesthesia in the distribution of the maxillary branch of the right trigeminal nerve, moderate right peripheral type facial nerve palsy, and limb ataxia on the right side. Neither muscle weakness nor sensory disturbance was observed. Slight hyperreflexia was noted in the right extremities, and bilateral plantar responses were flexor. He showed wide-based ataxic gait and was unable to do tandem gait. Brain CT scans and magnetic resonance (MR) images revealed a mass lesion in the right pons to the right middle cerebellar peduncle with ring enhancement, suggestive of a "target" sign. Laboratory tests, including hematological and biochemical analyses, tumor markers, and antibodies, had normal values while the tuberculin reaction and QuantiFERON-TB Gold were strongly positive. Cerebrospinal fluid analysis revealed a slight increase in the protein level (76 mg/dl) with a normal cell count (2 per µl), and polymerase chain reaction-based tests and cultures were negative for Mycobacterium tuberculosis three times. Right subclavicular lymph node and right adrenal gland showed accumulation of fluorodeoxyglucose on positron emission tomography-CT, as did the mass lesion in the brainstem. These findings suggested a possibility of a metastatic malignant tumor or extrapleural tuberculoma. Because of the patient's religious belief, we were unable to perform a biopsy of the lymph node, and thus administered anti-tuberculous drugs. With treatment, his neurological symptoms such as facial palsy and ataxia improved steadily except for paradoxical worsening for the initial five days, and the gadolinium-enhanced lesion shrunk markedly. Follow-up MR images demonstrated that the lesions did not expand further for 9 months. From this course of treatment, we diagnosed the patient's tumor as brainstem tuberculoma. Brain tuberculoma sometimes resembles a malignant tumor, and it is therefore challenging to diagnose brainstem tuberculosis in cases without lung lesions. It is important to make a comprehensive diagnosis based on the patient's background, imaging, and course of treatment, and to treat brainstem tuberculoma promptly.

[Atypical skull base osteomyelitis suspected of spreading inflammation from the ear canal with unilateral multiple cranial neuropathy and cerebral infarctions].

A 76-year-old man, who had undergone surgery for esophageal cancer in 2010, presented to our hospital in April 2017 complaining of prolonged slight fever, loss of appetite, and dysphagia. Initial evaluation revealed a paralyzed left vocal cord, slight muscle weakness of the extremities, left facial paralysis, hoarseness, left sternocleidomastoid and trapezius muscle weakness, tongue deviation to the left, and left hypacusia-suggesting a diagnosis of Garcin's syndrome. Laboratory tests revealed increased white blood cells and C-reactive protein. Cerebrospinal fluid (CSF) analysis showed mild pleocytosis (predominantly polymorphonuclear cells), elevated protein, and low CSF/plasma glucose ratio. CT showed mild clival erosion, with no evidence of carcinoma recurrence. Brain contrast-enhanced MRI showed abnormal clival marrow, enhanced soft tissue and dura matter from the clivus to the atlantoaxial joint, enhanced soft tissue around the left ear canal, multiple cerebral infarctions in the left watershed zones, and left internal carotid stenosis. There was excessive ear wax and inflammation of the left external acoustic meatus but no otorrhea or otalgia. On the basis of his overall presentation, he was diagnosed with atypical skull base osteomyelitis due to external otitis. He was treated with antibiotic treatment that included ceftazidime for the Pseudomonas aeruginosa detected on bacterial cultures. He did not respond to treatment and died approximately 4 months later. Skull base osteomyelitis is thus an important differential diagnosis candidate after finding unilateral, multiple cranial neuropathy, underscoring the importance of prompt treatment when suspected.

Chronic Inflammatory Demyelinating Polyneuropathy With Concurrent Membranous Nephropathy: An Anti-paranode and Podocyte Protein Antibody Study and Literature Survey.

Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN. Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared. Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35-50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration. Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies.

A case of cerebrotendinous xanthomatosis mimicking the clinical phenotype of mitochondrial disease with a novel frame-shift mutation (c. 43_44 delGG) in CYP27A1 gene exon 1.

A 37-old-male with a history of early childhood mental retardation was admitted to our hospital. He experienced recurrent syncopes at 23 years old, and at age 35 gait disturbance and hearing impairment developed gradually and worsened over time. His grandparents were in a consanguineous marriage. He was of short stature and absent of tendon xanthomas. Neurological examinations revealed scanning speech, dysphagia, right sensorineural hearing loss, spasticity in both upper and lower extremities, and spastic gait. Tendon reflexes were brisk throughout, and Babinski and Chaddock reflexes were both positive bilaterally. Laboratory tests revealed elevated lactate and pyruvate concentrations in both serum and cerebrospinal fluid. Fluid attenuated inversion recovery magnetic resonance imaging showed high intensity lesions in the bilateral cerebellar hemispheres, pyramidal tracts in the brainstem, and internal capsules symmetrically. Brain magnetic resonance spectroscopy measurements revealed an elevated lactate/creatine plus phosphocreatine ratio and a decreased N-acetyl-aspartate/creatine plus phosphocreatine ratio in the cerebellum. At this point, mitochondrial diseases, particularly myoclonic epilepsy with ragged-red fibers (MERRF), to be the most likely cause. We performed a biopsy of his left biceps brachii muscle, showing variations in fiber size with occasional central nuclei and very few ragged-red fibers. Blood mitochondrial respiratory enzyme assays showed normal values with elevated citrate synthase activity, and mitochondrial DNA analyses for MERRF revealed no pathogenic mutations. We then explored other possibilities and detected an elevated serum cholestanol concentration of 20.4 µg/ml (reference value <4.0) and genetic analysis by direct sequencing method disclosed a novel frame-shift mutation (c. 43_44delGG) in CYP27A1 gene exon1, leading to a diagnosis of cerebrotendinous xanthomatosis (CTX). This case emphasizes importance of awareness of CTX as a possibility when patients present with clinical phenotypes mimicking mitochondrial diseases, but with negative results for muscle pathology or genetic analyses. The measurements of serum cholestanol concentrations might be useful in diagnosing such atypical cases.

[A case of paroxysmal sympathetic storm after acute disseminated encephalomyelitis and hypoxic encephalopathy responding to clonidine hydrochloride].

We report the case of a 17-year-old woman with paroxysmal sympathetic storm (PSS), which was successfully treated with clonidine hydrochloride. The patient was hospitalized for acute disseminated encephalomyelitis in June 2006. Dysphagia led to severe aspiration pneumonia in September 2006, and she suffered cardiopulmonary arrest. She survived but had severe brain damage, with her brain MRI showing diffuse hypoxic encephalopathy. From October 2006, she had several episodes of profound tachypnea (> 60/min), tachycardia (160 to 170 beats/min), hypertension (> 140 mmHg), hyperthermia (39°C), and decerebrate posturing. During the attacks, the levels of catecholamines in the patient's blood and urine were markedly elevated. Accordingly, a diagnosis of PSS associated with hypoxic encephalopathy was made. Her PSS clearly improved after the administration of clonidine hydrochloride (900 µg/day). This case suggests that clonidine hydrochloride, an α2 blocker, may be one therapeutic option for PSS.

Japanese and American ALS patient preferences regarding TIV (tracheostomy with invasive ventilation): a cross-national survey.

Substantial disparities in TIV utilization rates among ALS patients have been observed, with rates in Japan far exceeding rates in the United States. Our objective was to elicit national preferences and their determinants. We predicted more Japanese than American patients would desire TIV, as would sicker patients, those already using non-invasive interventions, and those with more positive mood and outlook. Patients were enrolled in five U.S. states and six Japanese regions. Eligible patients completed surveys during clinic visits (U.S.) or at home (Japan). Survey responses were in multiple-choice format and took about 15 min to complete. One hundred and fifty-six Americans and 66 Japanese patients participated. Contrary to expectations, Japanese patients were more likely to oppose TIV, as were those on 24-h NIV and patients who knew someone using TIV. Most Japanese and American patients with advanced respiratory impairment were undecided or opposed to TIV, while nearly 20% in both countries were in favor. Finally, patients who favored TIV or who were undecided had more energy, greater wish to live, and more sense of control over ALS management. In conclusion, factors other than patient preferences, such as neurologist preferences, caregiver attitudes and perhaps lack of advance planning, may influence probability of TIV utilization.

[Case of non-convulsive status epilepticus after influenza virus B infection].

A 24-year-old woman was referred to our hospital because of impaired consciousness after influenza virus B infection. Neurological examination revealed mild disturbance of consciousness without other neurological abnormalities. Laboratory tests showed elevated serum CRP, IL-6 and TNF-α levels. The level of IL-6 in the cerebrospinal fluid was also slightly elevated. Electroencephalography (EEG) disclosed almost continuous generalized spike and wave complexes and multiple spikes and wave complexes at 1.5-3 Hz. Brain MRI was normal. She was diagnosed as having influenza encephalopathy presenting non-convulsive status epilepticus (NCSE), and commenced methylprednisolone pulse therapy followed by prednisolone with gradual tapering. She was also treated with intravenous phenytoin and oral sodium valproate for NCSE. The next day, her consciousness level had improved. Although she became alert, epileptic discharges on EEG were still observed on the seventh hospital day, and levetiracetam was added. Then, her epileptic discharges almost completely disappeared on the twelfth hospital day. She was discharged without any neurological deficit. We consider this patient to be a case of transient NCSE due to influenza encephalopathy; alternatively, she may have epileptic traits and her NCSE may have been provoked by influenza virus infection.

TAR DNA-binding protein 43 pathology in a case clinically diagnosed with facial-onset sensory and motor neuronopathy syndrome: an autopsied case report and a review of the literature.

We report an autopsy case of a 48-year-old female clinically diagnosed with facial-onset sensory and motor neuronopathy (FOSMN) syndrome with TAR DNA-binding protein 43 (TDP-43) pathology. She developed paresthesia involving her whole face, right upper extremity and the right side of her upper trunk, followed by dysphagia, dysarthria, muscle atrophy and weakness with fasciculation in both upper extremities. Her symptoms showed a marked cranial and right-sided dominancy. She had anti-sulfoglucuronyl paragloboside (SGPG) IgG and anti-myelin-associated glycoprotein (MAG) IgG, and repeatedly showed limited response to immunotherapies. Her disease was essentially progressive, culminating in death due to respiratory failure three and a half years after onset. The autopsy revealed severe degeneration of the nuclei of the right trigeminal nerve and right facial nerve and widespread TDP-43-positive glial inclusions in the brainstem tegmentum. Neurons in the hypoglossal nerve nuclei were also shrunken and lost, with TDP-43-positive neuronal inclusions. Neuronal loss and gliosis in the anterior horn, predominantly in the cervical cord, were prominent with TDP-43-positive skein-like inclusions. Bilateral ventral roots were obviously atrophic. Spinal tract degeneration was also prominent in the ventral columns, essentially sparing the anterior corticospinal tracts at the cervical cord level. Additionally there was severe myelin pallor in the right spinal trigeminal tract and right fasciculus cuneatus of the cervical cord. The right spinal root ganglion showed numerous Nageotte's nodules and focal lymphocytic infiltration. The present case manifested FOSMN syndrome clinically, while the pathological findings suggested a motor neuron disease like TDP-43 proteinopathy and a possible involvement of immune-mediated neuropathy.