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Alexander disease (AxD) is a rare autosomal dominant astrogliopathy caused by mutations in the gene encoding for glial fibrillary acidic protein. AxD is divided into two clinical subtypes: type I and type II AxD. Type II AxD usually manifests bulbospinal symptoms and occurs in the second decade of life or later, and its radiologic features include tadpole-like appearance of the brainstem, ventricular garlands, and pial signal changes along the brainstem. Recently, eye-spot signs in the anterior medulla oblongata (MO) have been reported in patients with elderly-onset AxD. In this case, an 82-year-old woman presented with mild gait disturbance and urinary incontinence without bulbar symptoms. The patient died 3 years after symptom onset as a result of rapid neurological deterioration after a minor head injury. MRI showed signal abnormalities resembling angel wings in the middle portion of the MO along with hydromyelia of the cervicomedullary junction. Herein, we report the case of this patient with older adult-onset AxD with an atypical clinical course and distinctive MRI findings.

Introduction: There is brainstem atrophy with normal ageing. It is pertinent to determine, if this atrophy with ageing, is associated with significant alteration in the midbrain to pons ratio. Aim: To determine size and ratio of midbrain and pons area among adults and elderly. Materials and Methods: This cross-sectional, analytical study was done in a tertiary care hospital, S Nijalingappa Medical College, Bagalkot, Karnataka, India from January 2022 to March 2022, including 200 apparently healthy adult and elderly participants. They were divided into two groups, 100 men (M1 ≤50 years and M2 >50 years) and 100 women (F1 ≤50 years and F2 >50 years). Each underwent multiplanar T1 Magnetic Resonance Imaging (MRI) of the brain. An experienced Radiologist identified midsagittal image, and measured midbrain and pons areas on that image. Mean and standard deviations of midbrain and pons area and midbrain to pons area ratio was estimated for each of the groups. Independent Sample t-test was used to determine significance of differences between groups. Results: A total of 200 participants were included in the study with mean age of 51 years and 3 months. The midbrain to pons area ratio among M2 and F2 groups ranged from 0.20 to 0.39, and in M1 and F1 groups it ranged from 0.23 to 0.47. Midbrain areas and midbrain to pons area ratio were significantly more among participants aged ≤50 years among both males (p-value=0.014 and 0.024) and females (p-value=0.011 and 0.032) in comparison with participants aged more than 50 years. Conclusion: Midbrain to pons area ratio decreases significantly in older age, and hence, age needs to be accounted for, while interpreting the ratio.

Aim: Multiple system atrophy (MSA) and CASPR2 antibody-associated disease bear their own characteristics. Case presentation: A 58-year-old woman presented with a 26 months history of uncoordinated gait and slurred speech. Her serum was positive for anti-CASPR2 antibodies, and MRI revealed atrophy of the brainstem and cerebellum. She underwent three plasma exchanges (PE) and received high doses of corticosteroids without any apparent effect. Her autonomic dysfunction improved after repetitive transcranial magnetic stimulation. Eventually, a diagnosis of MSA-cerebellar phenotype(MSA-C) was made. Conclusion: With increased availability of tools for neuron antibody detection, physicians need to be aware of the possibility that antibodies may accompany other diseases. This report underscores the modern dilemmas caused by available and extensive neuron antibody testing.

Abstract Background and objectives Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is an effective tool for distinguishing Parkinson's disease (PD) from other diseases accompanied by parkinsonism. Unlike other Parkinsonian diseases, in PD, MIBG accumulation in the heart tends to decrease. However, previous studies have reported that a decrease in MIBG accumulation also occurs in progressive supranuclear palsy (PSP). Thus, we analyzed the relationship between the degree of MIBG accumulation decrease, clinical symptoms, and brainstem atrophy in PSP. Methods We retrospectively collected data from patients who underwent MIBG myocardial scintigraphy and compared MIBG indices (heart to mediastinum [H/M] ratio, washout rate) between subjects with PSP and other diseases including PD. In addition, we evaluated the relationship between clinical characteristics, MIBG accumulation, and brainstem atrophy in patients with PSP. Results Patients with PSP had a significantly lower early H/M ratio compared with multiple system atrophy with predominant parkinsonism (MSA-P) patients, and a control group. In PSP patients there was a correlation between the decrease in delay H/M ratio, atrophy of the pons, and clinical severity as evaluated by Hoehn and Yahr score. Conclusion Unlike in PD, PSP patients exhibited a mild decrease in MIBG accumulation in MIBG myocardial scintigraphy, which may be related to brainstem atrophy. Highlights • Analysis of MIBG accumulation in the heart in progressive supranuclear palsy. • Progressive supranuclear palsy showed mild MIBG accumulation decrease in the heart. • MIBG accumulation decrease correlated with clinical severity and pons area atrophy. • MIBG accumulation decrease might reflect impairment of central autonomic function. [ABSTRACT FROM AUTHOR]

The intrathecal methotrexate is used in various hematological neoplasms that involves the central nervous system. The description of neurotoxicity has been performed predominantly in the pediatric population for decades, with a clinical spectrum mostly subacute and reversible, since focal neurological deficit until progressive and irreversible encephalopathy. The changes in magnetic resonance in most reports have been leukoencephalopathy and occasionally cerebellar lesions have been described, however there are no reports of brainstem and cerebellum atrophy. We present the case of a 55-year-old woman who was diagnosed with diffuse B-cell non-Hodgkin lymphoma treated with intravenous rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone and intrathecal methotrexate chemotherapy cycles at recurrent doses due to suspicion of cerebral infiltration of the disease, with subsequent clinical symptoms an radiologic findings similar to brainstem and cerebellum atrophy. Methotrexate neurotoxicity affected multiple regions of the brain causing atrophy and was related to the clinical syndrome as irreversible sequelae. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are central nervous system (CNS) inflammatory demyelinating disorders. It is clinically important to distinguish MS from NMOSD, as treatment and prognosis differ. Brainstem involvement is common in both disorders.Purpose: To investigate whether the patterns of brainstem atrophy on volumetric analysis in MS and NMOSD were different and correlated with clinical disability.Study Type: Case-control cross-sectional study.Subjects: In all, 17 MS, 13 NMOSD, and 18 healthy control (HC) subjects were studied.Field Strength/sequence: T1 -weighted and T2 w spin-echo images were acquired with a 3T scanner.Assessment: Semiautomated segmentation and volumetric measurement of brainstem regions were performed. Anatomical information was obtained from whole brain T1 w images using a 3D magnetization-prepared rapid gradient-echo (MPRAGE) imaging sequence (TR/TE/T: 7.0/3.2/800 msec, voxel size: 1 × 1 × 1 mm3 , scan time: 10 min 41 sec).Statistical Tests: Independent samples t-test, Mann-Whitney U-test, partial correlation, and multiple regression analysis.Results: Baseline characteristics were similar across the three groups, without significant difference in disease duration (P = 0.354) and EDSS score (P = 0.159) between MS and NMOSD subjects. Compared to HC, MS subjects had significantly smaller normalized whole brainstem (-5.2%, P = 0.027), midbrain (-8.3%, P = 0.0001), and pons volumes (-5.9%, P = 0.048), while only the normalized medulla volume was significantly smaller in NMOSD subjects compared to HC (-8.5% vs. HC, P = 0.024). Normalized midbrain volume was significantly smaller in MS compared to NMOSD subjects (-5.0%, P = 0.014), whereas normalized medulla volume was significantly smaller in NMOSD compared to MS subjects (-8.1%, P = 0.032). Partial correlations and multiple regression analysis revealed that smaller normalized whole brainstem, pons, and medulla oblongata volumes were associated with greater disability on the Expanded Disability Status Scale (EDSS), Functional System Score (FSS)-brainstem and FSS-cerebellar in NMOSD subjects.Data Conclusion: Differential patterns of brainstem atrophy were observed, with the midbrain being most severely affected followed by pons in MS, whereas only the medulla oblongata was affected in NMOSD.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1601-1609. [ABSTRACT FROM AUTHOR]

• Alexander's Disease (AD) is caused by heterozygous variants in the GFAP gene. • AD is considered a gain-of-function disease with excess production of GFAP protein. • We describe a case of acute adult-onset AD (AOAD) following alcohol exposure. • Acute alcohol induces GFAP protein expression, leading to a toxic GFAP environment. • Acute alcohol exposure may cause acute AOAD. [ABSTRACT FROM AUTHOR]

Abstract: A 1-year-old male began suffering from West syndrome at 3months of age, when electroencephalography revealed hypsarrhythmia accompanied by a periodic, brief suppression phase. The administration of adrenocorticotropic hormone was partially effective for stopping the condition, and the seizure type evolved into brief tonic seizures at 6months. Thereafter, progressive atrophy of the brain became evident by 9months of age, predominantly at the brainstem and cerebellum. Severe hypomyelination of the cerebral white matter was revealed at the age of 1year, and a de novo heterozygous mutation in the SPTAN1 gene was confirmed. The patient showed severely impaired psychomotor development, and had gained no visual attention. These findings contribute to the characterization of this recently established entity and facilitate the identification of further patients. [Copyright &y& Elsevier]

The article describes the clinical features, natural history, genetics and management of the Wolfram syndrome (WS). It discusses the management of children with diabetes mellitus as part of WS. The clinical manifestations of WS are listed, including diabetes mellitus, optic atrophy, diabetes insipidus, deafness, neurological symptoms, renal tract abnormalities, psychiatric disorders and gonadal disorders. A discussion of several cases of WS in children is presented.

We investigated whether the brainstem is affected by the pathologic process of sporadic Creutzfeldt-Jakob disease (sCJD), with particular attention to brainstem atrophy, neuronal loss, pyramidal tract degeneration, and prion protein (PrP) deposition, in 33 patients with sCJD. Brainstem atrophy, particularly in the pontine base, was relatively prominent in patients with disease of unusually prolonged duration. Neuronal loss and pyramidal tract degeneration were also identified in some but not all patients with prolonged disease. Neuronal loss was relatively prominent in the pontine nucleus and less so in the substantia nigra and inferior olivary nucleus; motor nuclei of the brainstem tegmentum were well preserved. PrP deposition was present in the brainstem in all patients, and was identified predominantly in the substantia nigra, quadrigeminal body, pontine nucleus, and inferior olivary nucleus. PrP deposition was less prominent in the red nucleus and tegmentum of the pons and medulla oblongata. PrP deposition occurred least or not at all in the pyramidal tract. The density of PrP deposition in the sCJD brainstem was not associated with disease duration or neuronal degeneration until the late stage. Our results show that atrophy, neuronal loss, and pyramidal tract degeneration occur in the sCJD brainstem, particularly in patients with an unusually prolonged disease course. These findings are not associated directly with PrP deposition and may reflect end-stage sCJD. No VV1, VV2, or MV2 cases were included in our study; however, we suggest that widespread and relatively stereotypic PrP deposition is a consistent pathologic feature of sCJD, at least in MM1 sCJD patients. Although accumulation of PrP in the brainstem appears to be an early pathologic event in sCJD, and may remain into the late disease stage, the brainstem remains relatively resistant to the pathologic process of sCJD. [ABSTRACT FROM AUTHOR]

Cranial computed tomograms of 12 patients with proven Wilson's disease were correlated with clinical disturbances. CT abnormalities occurred only in the eight patients with neurological manifestations. The presence of atrophy and low density lesions of the basal ganglia shown on CT correlated well with clinical signs of extrapyramidal dysfunction. Cerebral atrophy and cerebellar cortical atrophy were only moderately related to the degree of intellectual dysfunction and ataxia, respectively; there were no specific clinical signs in cases with brainstem involvement. Abnormalities may be marked in scans taken within a year of neuropsychiatric symptoms, but the most severly abnormal CT scans occurred in patients with a relatively longer duration of untreated disease. Computed tomography provides the opportunity to follow the response of the abnormalities of the brain to cupruresis and can give some assistance in management. [ABSTRACT FROM AUTHOR]

A 43-year-old man without a previous episode of uveitis presented with slowly progressive neurological symptoms that appeared within the past year such as dysarthria, ataxic gait, and behavioral changes. Brain MRI findings showed atrophic lesions in the brainstem and cerebellum. Because these clinical symptoms and abnormal MRI findings indicated spinocerebellar degeneration as the initial diagnosis, he was admitted to our hospital. On admission, we noticed that he had non-neurological manifestations of Behçet disease, such as stomatitis, genital ulcers, and folliculitis. HLA-B51 was positive. He also showed pleocytosis (29 cells/mm 3 , predominantly mononuclear cells) and elevated cerebrospinal fluid (CSF) IL-6 levels (213 pg/ml), hence he was diagnosed with chronic progressive neuro-Behçet disease (CPNBD). The therapeutic effect of a high-dose intravenous methylprednisolone pulse (1,000 mg/day for 3 days) and methotrexate (maximum dosage, 16 mg/week) was poor against both neurological symptoms and CSF findings. Intravenous infliximab therapy (5 mg/kg, 2 weeks) dramatically decreased CSF IL-6 levels (13 pg/ml) but clinical symptoms remained unchanged. MRI findings of extensive cerebral atrophy and increased CSF IL-6 levels at the pretreatment time point reflected irreversible neurological involvement in CPNBD. For cases with progressive psychiatric symptoms and cerebellar ataxia in the early stage of the disease, skin manifestations should be examined immediately, CSF IL-6 levels measured, and immunosuppressive therapy initiated before CPNBD progresses to brainstem atrophy.