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We herein report the distribution of gray matter lesions on magnetic resonance imaging (MRI) in two patients with lymphomatosis cerebri (LC). In our patients, the fluid-attenuated inversion recovery sequence of brain MRI demonstrated a bilateral and diffuse high signal intensity, not only in the white matter but also in the thalamus, globus pallidus, putamen, and hippocampus. Among the deep gray matter, the caudate head and putamen (striatum) were relatively spared when compared with the globus pallidus, thalamus, and hippocampus. Interestingly, we found seven previous reports of similar MRI findings, with relative sparing of the striatum, in patients with LC. This finding may be characteristic of LC and help facilitate its diagnosis. Further investigations of a larger number of LC patients are necessary to confirm these findings.

Introduction: Brachiocephalic artery stenosis rarely causes right hemispheric infarction with associated left hemiparesis. To date, there have been no reported cases of stroke associated with brachiocephalic artery stenosis that were successfully treated with recombinant tissue-type plasminogen activator (rt-PA), alteplase. Case Report: An 80-year-old woman presented with left hemiparesis. Brain computed tomography showed no hemorrhage, and computed tomography angiography demonstrated brachiocephalic artery stenosis. Alteplase was administered based on a diagnosis of ischemic stroke. Brain magnetic resonance imaging showed multiple acute infarctions. Thereafter, the blood pressure of the right arm was found to be lower than that of the left arm. The patient’s neurological deficits gradually improved; she was eventually able to walk again and was thus discharged home. Conclusion: While the combination of left hemiparesis and a decrease in blood pressure in the right arm are well known in patients with stroke associated with Stanford type A aortic dissections, it may also occur in patients with stroke due to brachiocephalic artery stenosis. Unlike stroke associated with Stanford type A aortic dissections, stroke due to brachiocephalic artery stenosis may be treated with alteplase.

Background The behavioural variant of frontotemporal dementia (bvFTD) is the most common phenotype of frontotemporal lobar degeneration (FTLD). FTLD is divided into three main pathological subtypes: tau-positive FTLD (FTLD-tau), FTLD-TAR DNA-binding protein (TDP), and FTLD-Fused in sarcoma (FUS). At present, it is difficult to predict the underlying pathological subtypes of sporadic bvFTD before a patient's death. Methods We retrospectively investigated the clinical features of 34 Japanese patients with sporadic bvFTD, with or without motor neuron disease (MND), who had been pathologically diagnosed with FTLD. We examined whether, and how, the clinical features differed among Pick's disease, FTLD-TDP, and FTLD-FUS patients. Results Six of the 34 patients developed MND during the course of bvFTD. These six bvFTD-MND patients were all pathologically diagnosed with FTLD-TDP. The other 28 patients were composed of 12 FTLD-tau patients including 11 Pick's disease patients, 8 FTLD-TDP patients, and 8 FTLD-FUS patients. A comparison of the clinical features of the three pathological subtypes of the 33 patients demonstrated that the age at onset was significantly younger in FTLD-FUS patients than in Pick's disease or FTLD-TDP patients. Furthermore, while hyperorality and dietary changes in the early stage of the disease were present in approximately 40% of Pick's disease and FTLD-FUS patients, they were absent in FTLD-TDP patients. Conclusion The comorbidity of MND, a younger age at onset, and hyperorality and dietary changes in the early stage may be useful clinical features for predicting underlying pathological subtypes of sporadic bvFTD. The results of our study should be confirmed by prospective studies employing a larger number of cases.

Background: Although acute pancreatitis is listed among the exclusion criteria for the administration of recombinant tissue plasminogen activator according to the Japanese Guideline for the Management of Stroke, the co-occurrence of acute pancreatitis and acute ischemic stroke has not been investigated. The present study aimed to assess the incidence rate of acute pancreatitis in patients with acute ischemic stroke. Methods: This study consecutively enrolled all patients with ischemic stroke admitted to the Department of Neurology, JA Toride Medical Center between April 2014 and March 2016. Diagnosis of acute pancreatitis was made according to the revised Atlanta Classification of Acute Pancreatitis. We retrospectively analyzed serum amylase activity and the frequency of acute pancreatitis as a comorbidity of ischemic stroke. Results: A total of 411 ischemic stroke patients were included. Serum amylase activity was measured for 364 patients, 27 of whom presented with amylase activity exceeding the upper limit of normal. In two patients with serum amylase activity greater than three times-fold the upper limit of normal, computed tomography or transabdominal ultrasonography showed no characteristic findings of acute pancreatitis. No patient in the cohort met the diagnostic criteria for acute pancreatitis. Conclusions: Acute pancreatitis is a very rare comorbidity of acute ischemic stroke.

Based on previous reports, we propose a practical guide to choose dabigatran 150 mg twice daily or apixaban 5 mg twice daily for patients with atrial fibrillation. We recommend the use of dabigatran 150 mg twice daily for patients with atrial fibrillation who have a high risk of embolism (e.g., ischemic stroke on other oral anticoagulants, presence of left atrial appendage thrombus) and a low risk of bleeding. However, the prevalence of such patients with atrial fibrillation is considered low because patients with atrial fibrillation with a high risk of embolism usually have a high risk of bleeding. In most other patients with atrial fibrillation, the use of apixaban 5 mg twice daily should be considered.

Background Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei. Methods We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Asberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei–damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups. Results Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups. Limitations We did not assess the damage to the ascending projection fibers from the raphe nuclei. Conclusions Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.

A 61-year-old woman presented with a 1-month history of decreased activities of daily living. Magnetic resonance imaging revealed abnormal intensities of the bilateral frontal lobes and enhancement of the thickened dura matter. A biopsy of the dura mater revealed multinucleated giant cells. She had sinusitis and hematuria; she was diagnosed with granulomatosis with polyangiitis. Hypertrophic pachymeningitis (HPM) was considered to have interrupted the venous flow and caused vasogenic edema. Bilateral frontal lobe edema resulting from HPM due to granulomatosis with polyangiitis has not been reported. A biopsy and examination for other organ complications were useful for the diagnosis and treatment of our patient.

Because fungi usually spread from the paranasal sinuses to the orbital apex in invasive fungal sinusitis (IFS), IFS often presents as an orbital apex syndrome (OAS) characterized by dysfunction of cranial nerves II, III, IV, V1, and VI. We report a case of sphenoid sinus mucormycosis that presented as isolated retrobulbar optic neuropathy. A 94‐year‐old woman presented with acute blindness in the right eye. Examination revealed the absence of light perception and pupillary reflex in the right eye. Head MRI showed a mass in the right sphenoid sinus, which was contiguous with the right optic nerve. She underwent endoscopic surgery, and a histopathological diagnosis of mucormycosis was established. Treatment with intravenous liposomal amphotericin B reduced the size of the mass. She has survived for more than 1 year without recurrence. Clinicians should consider that IFS can present as isolated retrobulbar optic neuropathy.

A 58-year-old man consulted our hospital due to a 2-year history of dysarthria and a 1-month history of blepharospasm. In addition to the ataxic dysarthria and blepharospasm, a neurological examination demonstrated slight ataxia of the trunk and lower limbs. Brain MRI demonstrated atrophy of the upper portion of the cerebellar vermis. Gene analysis established a diagnosis of spinocerebellar ataxia type 31 (SCA31). Single photon emission computed tomography (SPECT) with the three-dimensional stereotaxic ROI template (3DSRT) software program demonstrated hyperperfusion in the lenticular nucleus and thalamus. Although the association between SCA31 and blepharospasm in our patient remains unclear, we considered that this combination might be more than coincidental.

The behavioural variant of frontotemporal dementia (bvFTD) is the most common phenotype of frontotemporal lobar degeneration (FTLD). FTLD is divided into three main pathological subtypes: tau-positive FTLD (FTLD-tau), FTLD-TAR DNA-binding protein (TDP), and FTLD-Fused in sarcoma (FUS). At present, it is difficult to predict the underlying pathological subtypes of sporadic bvFTD before a patient's death.We retrospectively investigated the clinical features of 34 Japanese patients with sporadic bvFTD, with or without motor neuron disease (MND), who had been pathologically diagnosed with FTLD. We examined whether, and how, the clinical features differed among Pick's disease, FTLD-TDP, and FTLD-FUS patients.Six of the 34 patients developed MND during the course of bvFTD. These six bvFTD-MND patients were all pathologically diagnosed with FTLD-TDP. The other 28 patients were composed of 12 FTLD-tau patients including 11 Pick's disease patients, 8 FTLD-TDP patients, and 8 FTLD-FUS patients. A comparison of the clinical features of the three pathological subtypes of the 33 patients demonstrated that the age at onset was significantly younger in FTLD-FUS patients than in Pick's disease or FTLD-TDP patients. Furthermore, while hyperorality and dietary changes in the early stage of the disease were present in approximately 40% of Pick's disease and FTLD-FUS patients, they were absent in FTLD-TDP patients.The comorbidity of MND, a younger age at onset, and hyperorality and dietary changes in the early stage may be useful clinical features for predicting underlying pathological subtypes of sporadic bvFTD. The results of our study should be confirmed by prospective studies employing a larger number of cases.

A 74-year-old right-handed woman without cognitive impairment suddenly developed nonfluent aphasia. Brain MRI showed acute infarction in the right frontal lobe and insula without involvement of the corpus callosum. A neurological examination demonstrated not only transcortical motor aphasia, but also ideomotor apraxia and right hand predominant constructional apraxia (CA). To date, right hand predominant CA has only been reported in patients with corpus callosum lesions. The right hand predominant CA observed in our patient may be associated with the failure to transfer information on the spatial structure from the right hemisphere to the motor cortex of the left hemisphere.

We investigated the pathological features of frontotemporal lobar degeneration (FTLD) with fused in sarcoma protein (FUS) accumulation (FTLD-FUS) in the Japanese population. Only one out of nine FTLD-FUS cases showed pathology that corresponds to atypical FTLD with ubiquitin-positive inclusions (aFTLD-U). Five were basophilic inclusion body disease (BIBD) and two were neuronal intermediate filament inclusion disease. The last case was unclassifiable and was associated with dystrophic neurites (DNs) as the predominant FUS pathology. The results of this study indicate an ethnic difference from western countries. In Japan, BIBD is the most common subtype of FTLD-FUS and aFTLD-U is rare, a finding which contrasts with aFTLD-U being the most common form in western countries. Immunohistochemical analyses of these FTLD-FUS cases reveal that FUS abnormally accumulated in neuronal cytoplasmic inclusions (NCIs) and DNs has an immunohistochemical profile distinct from that of normal, nuclear FUS. NCIs and DNs are more readily stained than the nuclei by antibodies to the middle portion of FUS. Antibodies to the carboxyl terminal portion, on the other hand, stain the nuclei more readily than NCIs and DNs. Such an immunohistochemical profile of NCIs and DNs was similar to that of cytoplasmic granular FUS staining which we previously reported to be associated with dendrites and synapses. Redistribution of FUS from the nucleus to the cytoplasm could be associated with the formation of abnormal FUS aggregates in FTLD-FUS.

Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is a neurodegenerative disease characterized by postural instability and vertical gaze palsy, but the clinical diagnosis of PSP-RS is often difficult in the early stage of the disease. A 64-year-old male experienced frequent falls, followed by dysarthria and dysphagia. Neurological examination at age 64 demonstrated vertical gaze palsy, dysarthria, dysphagia, and retropulsion. At that time, while brain MRI demonstrated no apparent abnormalities, SPECT showed the reduction of the cerebral blood flow in the thalamus as well as the medial frontal lobe cortices. The patient was diagnosed with probable PSP-RS, and died at age 70. On postmortem examination, there were abundant tuft-shaped astrocytes, neurofibrillary tangles, coiled bodies, and argyrophilic threads in the brain, establishing the diagnosis of PSP-RS. Our definite PSP-RS case suggests that thalamic hypoperfusion may provide helpful evidence to support a diagnosis of PSP-RS in the early stage of the disease.

A 61-year-old Japanese woman presented with a headache and appetite loss lasting for nine days and was admitted to our hospital, where she was diagnosed with pneumococcal meningitis associated with acute sphenoid sinusitis. While the administration of meropenem and dexamethasone ameliorated the meningitis, right third and sixth nerve palsy suddenly developed 10 days after admission. CT angiography subsequently demonstrated an aneurysm in the cavernous portion of the right internal carotid artery. This is the first reported case of sphenoid sinusitis simultaneously complicated by both pneumococcal meningitis and an infectious aneurysm in the intracavernous carotid artery.

Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome.

Although progressive multifocal leukoencephalopathy (PML) cases showing responses to mefloquine therapy have been reported, the efficacy of mefloquine for PML remains unclear. We report on the failure of mefloquine therapy in two Japanese patients with PML unrelated to human immunodeficiency virus. One of the patients was a 47-year-old male who had been treated with chemotherapy for Waldenstrom macroglobulinemia, and the other was an 81-year-old male with idiopathic CD4 + lymphocytopenia. Diagnosis of PML was established based on MRI findings and increased JC virus DNA in the cerebrospinal fluid in both patients. Mefloquine was initiated about 5months and 2months after the onset of PML, respectively. During mefloquine therapy, clinical and radiological progression was observed, and JC virus DNA in the cerebrospinal fluid was increased in both patients. Both patients died about 4months and 2months after initiation of mefloquine, respectively. Further studies are necessary to clarify the differences between mefloquine responders and non-responders in PML.

High fever, severe neck pain and neck stiffness can result from meningitis. We report a case of pneumococcal pyomyositis of the neck muscles. A 72-year-old man developed high fever and severe neck pain. His chief complaint mimicked bacterial meningitis. Although his condition was initially suspected to be bacterial meningitis, his cerebrospinal fluid did not show pleocytosis. MRI showed areas of high intensity in the posterior deep neck muscles on short tau inversion recovery (STIR) sequences and gadolinium-enhanced T1-weighted images. Pneumococcal myositis should therefore be included in the differential diagnosis of severe neck pain with fever.

A 79-year-old man presented with a slowly progressive gait disturbance. Brain MRI demonstrated ventriculomegaly and the hummingbird sign. A lumbar puncture showed no abnormalities of the cerebrospinal fluid. The improvement of the gait disturbance after the ventriculoperitoneal shunt led to a diagnosis of idiopathic normal pressure hydrocephalus. Interestingly, postoperative brain MRI demonstrated the disappearance of not only ventriculomegaly, but also the hummingbird sign. The disappearance of the hummingbird sign suggests that an increase in the cerebrospinal fluid in the lateral and third ventricles could cause the compression of the superior surface of the midbrain tegmentum, which manifests as the hummingbird sign.

Choreoathetoid involuntary movements are rarely reported in patients with frontotemporal lobar degeneration (FTLD), suggesting their exclusion as a supportive feature in clinical diagnostic criteria for FTLD. Here, we identified three cases of the behavioral variant of frontotemporal dementia (bvFTD) that display chorea with fused in sarcoma (FUS)-positive inclusions (FTLD-FUS) and the basophilic inclusion body disease (BIBD) subtype. We determined the behavioral and cognitive features in this group that were distinct from other FTLD-FUS cases. We also reviewed the clinical records of 72 FTLD cases, and clarified additional clinical features that are predictive of the BIBD pathology. Symptom onset in the three patients with chorea was at 44.0 years of age (±12.0 years), and occurred in the absence of a family history of dementia. The cases were consistent with a clinical form of FTD known as bvFTD, as well as reduced neurological muscle tone in addition to chorea. The three patients showed no or mild parkinsonism, which by contrast, increased substantially in the other FTLD cases until a later stage of disease. The three patients exhibited severe caudate atrophy, which has previously been reported as a histological feature distinguishing FTLD-FUS from FTLD-tau or FTLD-TAR DNA-binding protein 43. Thus, our findings suggest that the clinical feature of choreoathetosis in bvFTD might be associated with FTLD-FUS, and in particular, with the BIBD subtype.

A 30-year-old Japanese woman without relevant family history presented with a behavioral abnormality followed by motor weakness about 14 years later. The patient died at age 45. Post mortem examination revealed degeneration of the frontal and temporal lobes, as well as lower motor neurons in the brainstem and spinal cord. These features were reported previously as being consistent with a diagnosis of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral sclerosis (ALS). In the present study, we show abundant fused in sarcoma (FUS)-positive dystrophic neurites but only a few neuronal cytoplasmic inclusions in the frontal and temporal cortices. TAR DNA-binding protein 43 (TDP-43)-positive inclusions were absent in the cerebrum. However, TDP-43-positive inclusions were present in the lower motor neurons of the brainstem and spinal cord. To our knowledge, this is the first report of a case in which FTLD-FUS pathology is of a dystrophic neurites-predominant type and FTLD-FUS is associated with ALS-TDP.

Progressive nonfluent aphasia (PNFA) is a clinical subtype of frontotemporal lobar degeneration (FTLD). FTLD with tau accumulation (FTLD-tau) and FTLD with TDP-43 accumulation (FTLD-TDP) both cause PNFA. We reviewed clinical records of 29 FTLD-TDP cases in the brain archive of our institute and found only one case of PNFA. The patient was an 81-year-old male at death. There was no family history of dementia or aphasia. He presented with slow, labored and nonfluent speech at age 75. Behavioral abnormality and movement disorders were absent. MRI at age 76 demonstrated atrophy of the perisylvian regions, including the inferior frontal gyrus, insular gyrus and superior temporal gyrus. The atrophy was more severe in the left hemisphere than the right. On post mortem examinations, neuronal loss was evident in these regions as well as in the substantia nigra. There were abundant TDP-43-immunoreactive neuronal cytoplasmic inclusions and round or irregular-shaped structures in the affected cerebral cortices. A few dystrophic neurites and neuronal intranuclear inclusions were also seen. FTLD-TDP showing PNFA seems to be rare but does exist in Japan, similar to that in other countries.

Clinical information on familial amyotrophic lateral sclerosis (FALS) with Gly72Ser mutation in the Cu/Zn superoxide dismutase-1 (SOD1) gene has been limited and autopsy findings remain to be clarified. We describe one Japanese family with ALS carrying Gly72Ser mutation in the SOD1 gene, in which autopsy was performed on one affected member. The autopsied female patient developed muscle weakness of the left thigh at age 66 and showed transient upper motor neuron signs. She died of respiratory failure 13 months after onset without artificial respiratory support. There were no symptoms suggesting bladder or rectal dysfunction throughout the clinical course. Her brother with ALS was shown to have Gly72Ser mutation in the SOD1 gene. Histopathologically, motor neurons were markedly decreased throughout the whole spinal cord, whereas corticospinal tract involvement was very mild and was demonstrated only by CD68 immunohistochemistry. Degeneration was evident in the posterior funiculus, Clarke's nucleus, posterior cerebellar tract, and Onuf's nucleus. Neuronal hyaline inclusions were rarely observed in the neurons of the spinal cord anterior horn including Onuf's nucleus, and were immunoreactive for SOD1. To date, neuron loss in Onuf's nucleus has hardly been seen in ALS, except in the patients showing prolonged disease duration with artificial respiratory support. Involvement of Onuf's nucleus may be a characteristic pathological feature in FALS with Gly72Ser mutation in the SOD1 gene.

Nasu-Hakola disease is an autosomal recessively inherited disease characterized by lipomembranous polycystic osteodysplasia and sclerosing leukoencephalopathy. While white matter lesions prominent in the brain have been reported in the literature, gray matter lesions have not received particular attention. In this study, we examined three autopsy cases of Nasu-Hakola disease in order to focus specifically on gray matter lesions. The ages at onset of the three cases were 20, 23 and 29 years, and the disease durations were 29, 19 and 8 years, respectively. In addition to characteristic degeneration in the cerebral white matter, such as demyelination with conspicuous fibrillary gliosis and axonal changes, all three cases showed overt pathology in the gray matter. Neuronal loss with gliosis in the thalamus (particularly in the dorsomedial nucleus and anterior nucleus), caudate nucleus, putamen and substantia nigra was prominent in all cases, and the severity corresponded to the disease duration. The cerebral cortices were relatively preserved in all cases. One case showed neuronal loss and gliosis in the gray matter of the hippocampus, possibly due to repeated episodes of epileptic convulsions. These gray matter pathologies are considered to be responsible for some of the clinical manifestations of the disease, including extrapyramidal symptoms.

Basophilic inclusions (BIs) are the pathological feature in a subset of frontotemporal lobar degeneration (FTLD), sporadic amyotrophic lateral sclerosis (SALS) and familial ALS (FALS) cases. Mutations in the fused in sarcoma (FUS) gene have been recently identified as the cause of FALS type 6. FUS-immunoreactive (ir) inclusions are consistently found in cases of FTLD with BIs, but the association between ALS cases with BIs and FUS accumulation is still not well understood. In this study, we immunohistochemically analyzed the autopsied case of FALS with BIs using anti-FUS antibodies. The case was a 42-year-old woman who developed proximal weakness of the bilateral upper limbs, followed by weakness of other parts including the bulbar regions, and died at age 45. Since this case is a member of a family with FALS harboring the R521C mutation of the FUS gene, she may have carried the same FUS mutation. Histopathologically, neuronal loss was evident in the motor system and other areas including the cuneate nucleus of the medulla oblongata. BIs appeared in the brain stem, cerebellum and anterior horn of the lumbar cord. FUS-ir neuronal cytoplasmic inclusions, glial cytoplasmic inclusions and dystrophic neurites were more abundantly and widely occurring than BIs, especially in the cuneate nucleus and globus pallidus. These findings support the idea that both BIs and FUS-ir structures are pathological hallmarks of a subset of ALS cases.

Transactivation response (TAR) DNA-binding protein of Mr 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathy. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role for the pathological process. In cultured cells, transfected C-terminal fragments of TDP-43 are more prone to form aggregates than full-length TDP-43. Transfecting the C-terminal fragment of TDP-43 harboring pathogenic mutations of TDP-43 gene identified in familial and sporadic ALS cases into cells enhanced the aggregate formation. Furthermore, we found that methylene blue and dimebon inhibit aggregation of TDP-43 in these cellular models. Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics.

Pseudopolyneuritic form of ALS is a subtype of ALS characterized by distal weakness of the unilateral lower limb and absence of Achilles tendon reflex (ATR) at disease onset. Recognition of this form of ALS is important for clinicians because the combination of distal weakness of the lower limb and absence of ATR usually suggests peripheral neuropathy. We reviewed the clinical records of 42 autopsy-proven sporadic ALS cases and found three cases that showed onset of weakness of the unilateral lower limb with distal dominance and absence of ATR. The disease duration in the three cases was 2, 3 and 19 years, respectively. The clinical features of the patient with a course of 19 years had been restricted to lower motor neuron signs. Histopathologically, consistent findings in the three cases were severe motor neuron loss throughout the whole spinal cord, with relative preservation of the hypoglossal nucleus. Reflecting this finding, TDP-43-positive neuronal cytoplasmic inclusions in the spinal cord were sparse in two cases, and absent in a third. In the patient showing a clinical course of 19 years, mild corticospinal tract degeneration appeared to correspond to the absence of upper motor neuron signs and prolonged disease duration. In this case only, Bunina bodies were not demonstrated. In this study, we clarified the clinical and pathological heterogeneity of this form of ALS.

Metastatic CNS lymphoma usually manifests as pachymeningeal or leptomeningeal infiltrates, and periventricular dissemination is rare. A 70-year old man first noticed a mass in the left supraclavicular fossa, and then presented with bilateral parkinsonism, followed by consciousness disturbance. Fluid attenuated inversion recovery (FLAIR) image of brain MRI demonstrated hyperintensities at the parenchyma around the lateral ventricle, third ventricle, and fourth ventricle. Gadolinium-enhanced T1-weighted image demonstrated enhancement along the whole wall of the ventricle. Biopsy of the left supraclavicular lymph nodes established a diagnosis of diffuse large B-cell lymphoma. The patient died of multiple organ failure about 5 months after the onset. Autopsy disclosed periventricular dissemination of lymphoma cells that was most severe around the lateral ventricle. We considered that the lymphoma cells entered the ventricular system through the choroid plexus of the lateral ventricle, followed by dissemination of the periventricular parenchyma.