Clinical Features and Neuroimaging Findings of Neuropil Antibody-Positive Idiopathic Sporadic Ataxia of Unknown Etiology.

Idiopathic sporadic ataxia (ISA) is the clinical term for nonfamilial ataxia with adult-onset and a slowly progressive course. However, immune-mediated cerebellar ataxia cannot be completely excluded from ISA. The current study investigated the neuropil antibodies against cell-surface antigens and clarified the clinical features and neuroimaging findings of patients with these antibodies. Using tissue-based immunofluorescence assays (TBAs), we examined antibodies against the cerebellum in serum samples from 67 patients who met the ISA diagnostic criteria, including 30 patients with multiple system atrophy with predominant cerebellar features (MSA-C) and 20 patients with hereditary ataxia (HA), and 18 healthy control subjects. According to the TBA results, we divided subjects into three groups: subjects positive for neuropil antibodies, subjects positive for intracellular antibodies only, and subjects negative for antibodies. We compared clinical features and neuroimaging findings in ISA patients among these three groups. The prevalence of neuropil antibodies in ISA (17.9%) was significantly higher than that in MSA-C (3.3%), HA (0%), or healthy subjects (0%). The neuropil antibody-positive ISA patients showed pure cerebellar ataxia more frequently than the other ISA patients. Two neuropil antibody-positive patients showed significant improvement of cerebellar ataxia after immunotherapy. We detected neuropil antibodies in 17.9% of ISA patients. Characteristic clinical features of neuropil antibody-positive ISA patients were pure cerebellar ataxia. Some cases of neuropil antibody-positive ISA responded to immunotherapy.

Autoimmune glial fibrillary acidic protein astrocytopathy associated with breast cancer: a case report.

BACKGROUND: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disorder characterized by the detection of autoantibodies that recognize GFAP in CSF. The pathogenesis of GFAP-A is poorly understood. Some patients had a neoplasm detected and GFAP expressed by neoplasms is plausible as immunogen triggering paraneoplastic neurological autoimmunity. CASE PRESENTATION: We report a case of 76-year-old female patient with GFAP-A complicated with breast cancer. She presented with altered consciousness, nuchal rigidity, speech disturbances, and weakness. Her clinical symptoms were improved by immunotherapy and cancer treatments. Immunohistochemical analysis showed that the restricted tumor expressed GFAP. The infiltration of CD3 + T cells were observed in the peritumoral and intratumoral areas. The most common infiltrating lymphocytes were CD8 + T cells. CD4 + T cells and CD20 + B cells were also observed in the predominant peritumoral area. CONCLUSIONS: These results suggest that GFAP-A may occur in a paraneoplastic neurological syndrome associated with breast cancer.

Case of adult-onset neuronal intranuclear hyaline inclusion disease with negative electroretinogram.

PURPOSE: To report the findings in a 72-year-old man with neuronal intranuclear hyaline inclusion disease (NIHID) with the negative-type electroretinogram (ERG) and without night blindness. METHODS: Standard ophthalmological examinations including the medical history, measurements of the best-corrected visual acuity and intraocular pressures, slit-lamp biomicroscopy, ophthalmoscopy, spectral-domain optical coherence tomography, fundus autofluorescence, and perimetry were performed. In addition, neurological and electrophysiological examinations were performed. RESULTS: NIHID was confirmed by skin biopsy. The ophthalmologic examinations revealed sluggish pupillary reflexes without visual disturbances and retinal abnormalities. The amplitudes of the dark-adapted 0.01 ERG was absent, and light-adapted 3 ERG and light-adapted 30 Hz flicker ERG were reduced in amplitude and delayed in implicit time. The rod system was more severely affected than the cone system, indicating that NIHID is classified as one of rod-cone dysfunction syndrome. The dark-adapted 3 ERG consisted of a markedly reduced b-wave with larger a-wave (negative ERG), but the amplitude of a-wave was smaller than normal. CONCLUSIONS: Since the ophthalmoscopical findings and the subjective visual functions may be essentially normal, the characteristic ERG abnormalities can be an important findings in adult-onset NIHID without night blindness.

A case of lithium intoxication induced by an antihypertensive angiotensin 1 subtype-specific angiotensin II receptor blocker in an elderly patient with bipolar disorder and hypertension.

Lithium carbonate is considered to be a first-line treatment for bipolar disorder; however, this drug has a narrow therapeutic window, and lithium intoxication is commonly induced by various drugs interaction and situations. We herein report a case of lithium intoxication induced by the administration of an antihypertensive agent targeting the angiotensin 1 (AT1) subtype of the angiotensin II receptor in a 65-year-old woman with a 40-year history of bipolar disorder type 1, and 1-year history of essential hypertension. Her bipolar disorder had been well-controlled with 600 mg/day of lithium carbonate for more than 10 years. She was later diagnosed with hypertension and the AT1 receptor blocker, azilsartan was thereafter administrated on a daily basis. After 3 weeks of azilsartan administration, she presented with progressive action tremor and showed a gradual deterioration of her physical state. Four months after the start of azilsartan administration, she presented with alternating episodes of diarrhea and constipation. Two weeks before admission to our hospital, she presented with mild consciousness disturbances, myoclonus, truncal ataxia, and appetite loss. She was diagnosed to have lithium intoxication based on an elevated serum lithium concentration of 3.28 mEq/l.It is therefore important to evaluate the serum lithium concentration after the administration of antihypertensive agents, and consider lithium-antihypertensive agent interactions when selecting antihypertensive agents in elderly patients receiving long-term lithium carbonate treatment.

[Two patients of immunotherapy-responsive autoimmune cerebellar ataxia fulfilled with criteria of multiple system atrophy].

We report two patients with autoimmune cerebellar ataxia who fulfilled the diagnostic criteria of multiple system atrophy (MSA) and responded to immunotherapies. Patient 1 was a 72-year-old man who was diagnosed with clinically probable MSA according to Movement Disorder Society criteria. Patient 2 was a 68-year-old man who was diagnosed with clinically established MSA according to Movement Disorder Society criteria. Both patients showed cerebellar ataxia, autonomic dysfunction, and pyramidal tract signs; however, they also had atypical clinical features. Patient 1 exhibited self-|limiting mild improvement of clinical symptoms and had inflammatory findings in his cerebrospinal fluid. Patient 2 showed a rapidly progressive clinical course. We therefore examined anti-neuronal antibodies using tissue-based immunohistochemical assays with frozen rat cerebellum sections. We detected autoantibodies that mainly reacted with the cytoplasm of Purkinje cells. The two patients then underwent immunotherapies, which led to substantial improvements in their clinical symptoms. Our findings indicate that some patients with autoimmune cerebella ataxia have clinical features that resemble MSA, and respond well to immunotherapies.

Anti-contactin-associated protein 1 antibody-positive nodopathy presenting with central nervous system symptoms.

Contactin-associated protein 1 (Caspr1) is widespread in both the peripheral and central nervous systems (CNS). However, anti-Caspr1 antibody-positive nodopathy associated with CNS symptoms has not previously been reported. In this case, a 69-year-old man presented with polyneuropathy and memory loss. The patient had negative myoclonus, positive myoclonus, and pseudoathetosis in the upper limbs, and we detected anti-Caspr1 antibodies in the serum and cerebrospinal fluid. Therefore, anti-Caspr1 nodopathy was diagnosed. After rituximab treatment, all symptoms of polyneuropathy, involuntary movements, and memory impairment improved. In conclusion, anti-Caspr1 antibodies might also affect the CNS; therefore, CNS symptoms of anti-Caspr1 nodopathy require attention.

Anti-N-methyl-d-aspartate receptor encephalitis preceded by meningitis lasting up to 60 days.

Long-lasting meningitis complicated by N-methyl-d-aspartate receptor (NMDAR) encephalitis has not been discussed widely in the literature. Herein, we present two cases of anti-NMDAR encephalitis preceded by meningitis. The patients had 60- and 22-day periods of preceding meningitis, which improved with intravenous methylprednisolone and plasmapheresis. No tumors were detected in either of the patients. Although meningitis preceding anti-NMDAR encephalitis is not rare, our patients, especially those who had it for a duration of 60 days, had longer durations of meningitis. This manuscript foregrounds that anti-NMDAR encephalitis might be included in the differential diagnosis of long-lasting meningitis.

Characteristics of Movement Disorders in Patients with Autoimmune GFAP Astrocytopathy.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is a type of autoimmune corticosteroid-responsive meningoencephalitis that occurs with or without myelitis. Movement disorders have been reported in GFAP-A patients but have not been characterized. In this study, we examined the characteristics of movement disorders in GFAP-A patients. We retrospectively reviewed clinical data from 87 consecutive patients with GFAP-A attending Gifu University Hospital in Japan. We compared the demographics, clinical features, cerebrospinal fluid characteristics, and neuroimaging findings from patients with and without movement disorders. Seventy-four patients (85%) had movement disorders, including ataxia (49%), tremor (45%), myoclonus (37%), dyskinesia (2%), opsoclonus (2%), rigidity (2%), myokymia (1%), and choreoathetosis (1%). GFAP-A patients with movement disorders were significantly older than those without. Movement disorders are therefore common in GFAP-A patients, and the main types of movement disorders observed in this population were ataxia, tremor, and myoclonus. These abnormal movements can serve as clinical features that facilitate the early diagnosis of GFAP-A. Elderly GFAP-A patients are more likely to have movement disorder complications than younger patients.

Autoimmune glial fibrillary acidic protein astrocytopathy resembling isolated central nervous system lymphomatoid granulomatosis.

We report two patients with meningoencephalomyelitis without evidence of extra central nervous system (CNS) involvement. Brain MRI showed linear perivascular radial gadolinium enhancement patterns and spinal cord MRI showed longitudinal extensive T2-hyperintensity lesions. Pathological findings from brain biopsies were angiocentric T-cell predominant lymphoid infiltrates that lacked Epstein-Barr virus-positive atypical B cells. The patients were initially suspected to have isolated CNS-lymphomatoid granulomatosis (LYG). Thereafter, glial fibrillary acidic protein (GFAP)-immunoglobulin G were detected in their cerebrospinal fluid. This finding suggested autoimmune GFAP astrocytopathy. We speculate there is a link between isolated CNS-LYG and autoimmune GFAP astrocytopathy.

[Approach from a Perspective of Autoimmune Cerebellar Ataxia].

Recently, the diagnostic criteria for idiopathic cerebellar ataxia (IDCA) have been proposed in Japan as a diagnosis to replace the clinical concept of cortical cerebellar atrophy, which was originally described as a neuropathological disorder. However, IDCA proposed in Japan may include various diseases such as multiple system atrophy with early stage, rare hereditary ataxias, and autoimmune-mediated cerebellar ataxia. We tackled this significant clinical challenge by detecting anti-cerebellar autoantibodies in patients' sera and identifying their target antigens. We detected anti-cerebellar autoantibodies in the sera of some patients diagnosed with IDCA in Japan. In the future, it will be necessary to confirm the efficacy of immunotherapy for anti-cerebellar autoantibody-positive cases among patients who were thought to be difficult to treat.

Brain Abscess Presenting as Prolonged Headache in a Patient with Amyotrophic Lateral Sclerosis under Mechanical Ventilation.

A 57-year-old woman with amyotrophic lateral sclerosis (ALS) receiving mechanical ventilation developed intractable right temporal headache. She was diagnosed with brain abscess secondary to chronic suppurative otitis media. In this case, the otitis media was caused by nasopharyngeal reflux associated with eustachian tube muscle weakness and a supine position. In addition, ALS patients under mechanical ventilation have a limited ability to convey their pain. Their complaints are often overlooked because many physicians do not know that pain is common in ALS. Physicians should recognize brain abscess as a severe complication of ALS and listen to the complaints of these patients.

Clinical characteristics of autoimmune GFAP astrocytopathy.

The clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy remain to be elucidated. We describe here the clinical features of 14 patients with GFAP astrocytopathy confirmed by detection of GFAP-IgG in cerebrospinal fluid (CSF). The novel findings of this study are as follows. First, over half of the patients presented with movement disorders (tremor, myoclonus, and ataxia), autonomic dysfunction (mainly urinary dysfunction), and hyponatremia. Second, most patients showed transient elevation of adenosine deaminase activity levels in CSF. Finally, some patients showed bilateral hyperintensities in the posterior part of the thalamus on brain magnetic resonance imaging.

[Distal-type Cervical Spondylolisthesis Muscular Atrophy in a Patient with Dupuytren Contracture: A Case Report].

We report the case of a 71-year-old man with impaired left finger extension. The presence of nodular fibrosing lesions in his palm suggested Dupuytren contracture as the diagnosis. However, detailed neurological examination revealed muscle weakness associated with C7-Th1 lesions, and needle electromyography revealed denervation within the same distribution. Therefore, the patient was diagnosed with distal-type cervical spondylolisthesis muscular atrophy complicated with Dupuytren contracture. Due to shared symptoms with impaired finger extension, the other two conditions can be overlooked in patients affected by both diseases. Detailed clinical investigation of nodular fibrosing lesions, muscle weakness at the C7-Th1 level, and needle electromyography findings facilitate differential diagnosis of Dupuytren contracture and distal-type cervical spondylolisthesis. (Received June 24, 2019; Accepted September 17, 2019; Published November 1, 2019).

[A Patient with Progressive Multifocal Leukoencephalopathy Who Developed Bálint Syndrome Improved by Combination Therapy Using Mefloquine and Mirtazapine].

We describe a 62-year-old man who developed subacute visual loss after cord blood stem cell transplantation for malignant lymphoma. Brain magnetic resonance imaging (MRI) showed bilateral hyperintense lesions in the occipital and parietal lobes. A diagnosis of progressive multifocal encephalopathy (PML) was established following brain biopsy and detection of JC virus (JCV) deoxyribonucleic acid (DNA) in the cerebrospinal fluid (CSF). He developed optic ataxia and visual inattention, and was then diagnosed as having Bálint syndrome. After he was treated with mefloquine and mirtazapine, his Bálint syndrome and, MRI findings improved and the copy number of JCV DNA in the CSF decreased. In summary, we demonstrate that patient with PML may develop Bálint syndrome and that combination therapy using mefloquine and mirtazapine may be an effective treatment. (Received August 23, 2018; Accepted November 29, 2018; Published March 1, 2019).

An autopsy-verified case of FTLD-TDP type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease.

Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes. Periodic sharp-wave complexes were not observed on the electroencephalogram. Brain diffusion MRI did not reveal abnormal changes. An easy Z score (eZIS) analysis for 99mTc-ECD-single photon emission computed tomography (99mTc-ECD-SPECT) revealed a bilateral decrease in thalamic regional cerebral blood flow (rCBF). PRNP gene analysis demonstrated methionine homozygosity at codon 129 without mutation. Cerebrospinal fluid (CSF) analysis showed normal levels of both 14-3-3 and total tau proteins. Conversely, prion protein was slowly amplified in the CSF by a real-time quaking-induced conversion assay. Her symptoms deteriorated to a state of akinetic mutism, and she died of sudden cardiac arrest, one year after symptom onset. Despite the SPECT results supporting a clinical diagnosis of MM2-thalamic-type sCJD, a postmortem assessment revealed that this was a case of FTLD-TDP type A, and excluded prion disease. Thus, this case indicates that whereas a bilateral decreasing thalamic rCBF detected by 99mTc-ECD-SPECT can be useful for diagnosing MM2-thalamic-type sCJD, it is not sufficiently specific. Postmortem diagnosis remains the gold standard for the diagnosis of this condition.

Preserved regional cerebral blood flow in the occipital cortices, brainstem, and cerebellum of patients with V180I-129M genetic Creutzfeldt-Jakob disease in serial SPECT studies.

Creutzfeldt-Jakob disease (CJD) with a causative point mutation of valine to isoleucine at codon 180 (V180I) is one of the major types of genetic CJD (gCJD) in Japan. V180I gCJD is rarely accompanied by a family history, and its clinical characteristics include late-onset, long disease duration, and edematous cortical hyperintensity in diffusion, fluid attenuate inversion and T2-weighted MRI. We performed serial imaging with single-photon emission computed tomography (SPECT) and MRI in three V180I gCJD cases over long-term observation. All cases were characterized by progressive dementia, parkinsonism, and the absence of cerebellar signs or cortical visual dysfunction in their clinical courses. Moreover, during the end-stage, SPECT findings showed preserved regional cerebral blood flow (rCBF) in the occipital cortices, brainstem, and cerebellum. Similarly, no apparent atrophy or increased signal intensities were observed in MRI images of the occipital and cerebellar regions. In conclusion, we report a decrease in rCBF predominantly in the frontal and temporal cortices during the early-stage, which became more widespread as the disease progressed. Importantly, rCBF was preserved in the occipital cortices, brainstem, and cerebellar regions until the end-stage, which may be distinct to V180I gCJD cases.