The predominance of "astrocytic" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on "astrocytic" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than "neuronal" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs ("gliopathy") should be more appreciated in future studies of NIID.

Prognosis after steroid pulse therapy and seasonal effect in acquired idiopathic generalized anhidrosis.

Acquired idiopathic generalized anhidrosis is a rare disease with unknown etiology. Sudden loss of sweating function adversely affects young patients' quality of life. Although systemic corticosteroid therapy is the most frequently reported treatment for the disease, its effectiveness is controversial because of the risk of recurrence. To assist clinical decision-making regarding whether to use steroids, we investigated the treatment responsiveness and recurrence rates in patients undergoing steroid pulse therapy and explored factors affecting these rates. We retrospectively collected data of 124 patients who received steroid pulse therapy to calculate the rate of responsiveness to the therapy. We also conducted a time-to-event analysis in a cohort of 57 patients who responded to steroid pulse therapy to estimate the recurrence rate after the therapy. As a result, the response and recurrence rates were 73% and 48%, respectively. Recurrence occurred within 1 year in most patients. The overall effectiveness of steroid pulse therapy was estimated to be 57% considering the recurrence rate. A delay from onset to treatment and younger age appeared to be negative factors for effectiveness. Moreover, we found a significant seasonal effect on both treatment and recurrence: autumn was the worst season for acquired idiopathic generalized anhidrosis in Japan. Our study revealed that steroid pulse therapy can be expected to be effective in half of treated patients. We recommend starting the therapy promptly after the diagnosis; however, it is also worth considering the season for treatment planning.

Polycystic subdural hygroma associated with immunoglobulin G4-related intracranial hypertrophic pachymeningitis: a case report.

BACKGROUND: Recent studies have examined hypertrophic pachymeningitis as an IgG4-RD. However, there are no reports of immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis with polycystic subdural hygroma. CASE PRESENTATION: A 56-year-old man presented to the hospital with complaints of a persistent, pulsatile, occipital headache and general malaise. Magnetic resonance imaging of the brain revealed hypertrophic pachymeningitis with polycystic subdural hygroma and hematoma. Based on the dural biopsy findings and exclusion of other diseases, the patient was diagnosed with immunoglobulin G4 (IgG4)-related hypertrophic pachymeningitis. IgG4-related diseases may cause subdural hygroma more commonly than other diseases that cause hypertrophic pachymeningitis. CONCLUSIONS: This is the first case report discussing polycystic subdural hygroma and hematoma with IgG4-related hypertrophic pachymeningitis.

Noncoding CGG repeat expansions in neuronal intranuclear inclusion disease, oculopharyngodistal myopathy and an overlapping disease.

Noncoding repeat expansions cause various neuromuscular diseases, including myotonic dystrophies, fragile X tremor/ataxia syndrome, some spinocerebellar ataxias, amyotrophic lateral sclerosis and benign adult familial myoclonic epilepsies. Inspired by the striking similarities in the clinical and neuroimaging findings between neuronal intranuclear inclusion disease (NIID) and fragile X tremor/ataxia syndrome caused by noncoding CGG repeat expansions in FMR1, we directly searched for repeat expansion mutations and identified noncoding CGG repeat expansions in NBPF19 (NOTCH2NLC) as the causative mutations for NIID. Further prompted by the similarities in the clinical and neuroimaging findings with NIID, we identified similar noncoding CGG repeat expansions in two other diseases: oculopharyngeal myopathy with leukoencephalopathy and oculopharyngodistal myopathy, in LOC642361/NUTM2B-AS1 and LRP12, respectively. These findings expand our knowledge of the clinical spectra of diseases caused by expansions of the same repeat motif, and further highlight how directly searching for expanded repeats can help identify mutations underlying diseases.

An autopsy report of three kindred in a Gerstmann-Sträussler-Scheinker disease P105L family with a special reference to prion protein, tau, and beta-amyloid.

INTRODUCTION: Gerstmann-Sträussler-Scheinker disease P105L (GSS105) is a rare variant of GSS caused by a point mutation of the prion protein (PrP) gene at codon 105 (proline to leucine substitution). It is clinically characterized by spastic paraparesis and dementia and histopathologically defined by PrP-plaques in the brain. This report describes a clinicopathological analysis of three autopsied kindred from a Japanese GSS105 family, plus a topological analysis of PrP, hyperphosphorylated tau (p-tau), and beta-amyloid (Aß). METHODS: Using paraffin-embedded sections, we applied histology and single- and multiple-labeling immunohistochemistry for PrP, p-tau, and Aß to the three cases. Comparative semi-quantitative analyses of tissue injuries and PrP-plaques were also employed. RESULTS: Case 1 (45 years old (yo)) and Case 2 (56 yo) are sisters, and Case 3 (49 yo) is the son of Case 2. Case 1 and Case 2 presented with spastic paraparesis followed by dementia, whereas Case 3 presented, not with spastic paraparesis, but with psychiatric symptoms. In Case 1 and Case 2, the brain showed tissue injuries with many PrP-plaques in the cerebral cortices, and the pyramidal tract showed myelin loss/pallor. In Case 3, the brain was least degenerated with a number of PrP-plaques; however, the pyramidal tract remained intact. In addition, p-tau was deposited in all cases, where p-tau was present in or around PrP-plaques. By double-labeling immunohistochemistry, the colocalization of p-tau with PrP-plaques was confirmed. Moreover in Case 2, Aß was deposited in the cerebral cortices. Interestingly, not only p-tau but also Aß was colocalized with PrP-plaques. In all cases, both three repeat tau and four repeat tau were associated with PrP-plaques. CONCLUSIONS: The clinicopathological diversity of GSS105, which is possible even in the same family, was ascertained. Not only p-tau but also Aß could be induced by PrP ("secondary degeneration"), facilitating the kaleidoscopic symptoms of GSS.

Fatal Familial Insomnia Initially Developing Parkinsonism Mimicking Dementia with Lewy Bodies.

We report a rare case of fatal familial insomnia in a 58-year-old man who initially developed parkinsonism, secondary dementia, and visual hallucinations that were suspected to be due to dementia with Lewy bodies. We evaluated the function of the striatum via dopamine transporter single-photon emission computed tomography (DAT SPECT) using 123I-ioflupane and found marked presynaptic dopamine dysfunction in the bilateral striatum. This is the first reported case in which the initial symptom of fatal familial insomnia was parkinsonism and in which the dopamine transporter function was evaluated by DAT SPECT.

The Clinical Features of Ischemic Stroke Patients for Whom Smoking Was Considered the Sole Risk Factor for Ischemic Stroke.

Objective The purpose of this study was to clarify the clinical features of ischemic patients for whom cigarette smoking was the sole risk factor for ischemic stroke. Methods Among the 1,329 patients (male, n=833; female, n=496) with acute ischemic stroke who were admitted to our hospital between April 2005 and September 2016, 346 (26%) were smokers [male, n=308 (36.9%); female, 38 (7.6%)]. In 42 (3.1%; male, n=41; female, n=1) cases, cigarette smoking was considered to be the sole risk factor for ischemic stroke. Data regarding gender, age, the clinical type of ischemic stroke, the National Institutes of Health Stroke Scale (NIHSS) score at the admission, the modified Rankin scale (mRS) scores before the onset and at discharge, the progression of symptoms, and the recurrence of infarction were investigated. Results The mean age of the 42 patients was 63.2±12.4 years (range, 26-86 years). The clinical types of ischemic stroke included atherothrombosis (n=19), lacunar (n=17), other type (n=2) and undetermined type (n=4). The median NIHSS score at the time of admission for ischemic stroke was 2 (interquartile range: IQR 1-4.25). The median mRS scores before the onset and at the discharge were 0 (IQR 0-0) and 1 (IQR 0-2), respectively. One patient had symptoms of progression; no patients had recurrence of infarction. Conclusion Our findings suggest that cigarette smoking alone may induce ischemic stroke; moreover, patients for whom smoking was the sole risk factor for ischemic stroke showed milder symptoms in comparison to patients with other risk factors; however, ischemic stroke was induced from youth. Since cigarette smoking has detrimental effects on the central nervous system, we suggest that people be encouraged to quit smoking in order to maintain good health.

Isolated Hypoglossal Paralysis Caused by Ischemic Infarction in the Centrum Semiovale.

In the present report, we discuss the case of a 66-year-old woman with isolated unilateral hypoglossal paralysis due to cerebral infarction in the centrum semiovale. To date, it has hardly been discussed where the corticolingual tract passes through in the centrum semiovale. Brain magnetic resonance imaging revealed a small ischemic infarction in the contralateral centrum semiovale. We could demonstrate a route of the corticolingual tract.

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery.

Evaluation of the correlation between severity of acquired idiopathic generalized anhidrosis and quality of life scores.

Symptoms of acquired idiopathic generalized anhidrosis (AIGA) include heat retention and/or heat stroke due to the effects of the disorder on the perspiration ability of the whole body under thermal environmental changes or exercise. Additionally, cholinergic urticaria can also occur in these patients. AIGA has a major impact on everyday life. However, the effects of AIGA severity on the quality of life (QOL) of the patients have not been sufficiently defined. The objective of this study was to evaluate the correlation between AIGA severity and QOL. Study subjects comprised 44 patients diagnosed with AIGA at three registered institutions. AIGA severity assessment was conducted and the Dermatology Life Quality Index (DLQI) questionnaire was administered. Correlations between AIGA severity and DLQI, as well as severity by DLQI subscale, were assessed. We found a positive correlation between total score of AIGA severity criteria and DLQI total scores (R = 0.720, P = 0.001). The impairment increased with the increase in AIGA severity (P < 0.01). In relation to the DLQI subscales, leisure (social and sporting activities) impairment was significantly higher for patients with severe AIGA than those with mild AIGA (P < 0.01). Comparing QOL for AIGA patients with that of patients with other dermatological disorders, it is possible that QOL impairment for AIGA patients is as severe as that for patients with atopic dermatitis. AIGA severity and DLQI are correlated and AIGA patients experience disruption of everyday life more broadly than conventionally perceived.

Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan.

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by an acquired impairment in total body sweating despite exposure to heat or exercise. Severe cases may result in heatstroke. Most cases of AIGA have been reported in Asia, especially in Japan. However, there is limited information on the epidemiology of this condition, and no diagnostic criteria or appropriate treatment options have been established. This guideline was developed to fill this gap. It contains information on the etiology, diagnosis, evaluation of disease severity and evidence-based recommendations for the treatment of AIGA. Appropriate treatment according to disease severity may relieve the clinical manifestations and emotional distress experienced by patients with AIGA.

A case of idiopathic pure sudomotor failure associated with prolonged high levels of serum carcinoembryonic antigen.

We report a case of idiopathic pure sudomotor failure (IPSF) in which serum carcinoembryonic antigen (CEA) levels elevated at onset, and remained high while anhidrosis lasted. We considered that changes in serum levels of CEA were related to the disease activity of IPSF.

[Neuroanatomy of Isolated Body Lateropulsion].

Axial body lateropulsion, a phenomenon where the body is pulled toward the side of the lesion, with tendency of falling down, is the well-known transient feature of lateral medullary syndrome. In some cases, axial body lateropulsion occurs without vestibular and cerebellar symptoms (isolated body lateropulsion:[iBL]). Patients with iBL have a lesion located in the spinocerebellar tract, descending lateral vestibulospinal tract, vestibulo-thalamic pathway, dentatorubrothalamic pathway, or thalamocortical fascicle. This review deals with the anatomic basis and clinical significance of iBL.

Evaluation of the Differences in the Effects of Antihypertensive Drugs on Blood Pressure Variability by 24-Hour Ambulatory Blood Pressure Monitoring in Chronic Cerebrovascular Disease.

BACKGROUND: It has been suggested that antihypertensive drug therapy is attributable to the lower blood pressure variability, we investigated the effects of 4 classes of antihypertensives on the blood pressure variability; in addition, we also compared the effects among 4 calcium channel blockers. METHODS: We measured the 24-hour blood pressure variability in 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, ß blocker, or calcium channel blocker. RESULTS: The daytime blood pressure variability treated with ß blockers (14.3 ± 3.1) was higher than that treated with an angiotensin receptor blockers (11.5 ± 3.1) or calcium channel blockers (12.6 ± 3.4) in patients with cerebrovascular disease (P < .05). In the analysis of the patient distribution of blood pressure variability, patients receiving ß blockers occurred more frequently in the higher blood pressure variability (P = .0023). Treatment with angiotensin receptor blockers and cilnidipine, which blocks N-type calcium channels, was shown to be more frequently associated with the lower blood pressure variability (P = .0202 and .0467). The mean blood pressure of patients grouped by distribution of blood pressure variability was found to be independent to blood pressure variability, for any of the antihypertensive drugs or calcium channel blockers examined. CONCLUSIONS: From the results, it is suggested that angiotensin receptor blocker and calcium channel blockers rather than ß blockers may be more favorable for blood pressure management in patients with cerebrovascular disease. Among the calcium channel blockers, cilnidipine may be more favorable than other calcium channel blockers.