Vision Loss in Subacute Sclerosing Panencephalitis: A Systematic Review of Case Reports and Case Series.

Vision loss is a presenting complaint in many patients with subacute sclerosing panencephalitis (SSPE). Data related to vision loss in SSPE is available only in the form of case reports. In this systematic review, we evaluated characteristics of vision loss, affected anatomic site, and patient course and outcome. We extracted data from four databases: PubMed, Embase, Scopus, and Google Scholar. The last search was done on October 26, 2022. We adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was registered with PROSPERO (CRD42022362652). Dyken's criteria were used for the diagnosis of SSPE. The data were recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool was used to assess the quality of data. The mean age of patients with SSPE was 17.9 years. Males outnumbered females (60:34). In 73 patients (76%), duration of illness/onset of vision loss was less than 6 months. In 76% patients (n = 73), visual manifestations appeared before encephalopathy. Involvement of the retina (58 of 96, 60.4%), optic nerve (9 of 96, 9.3%), or cerebral cortex (29 of 96, 30.2%) was responsible for vision loss. T2/fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) parieto-occipital hyperintensities were the most frequent (71.4%) neuroimaging abnormality. Retinal biopsy revealed similar findings revealed by brain histopathology. All patients died and became akinetic mute during the follow-up period, which ranged from a few weeks to a few years. In conclusion, retinal involvement was the most common cause of vision loss. Vision loss often precedes encephalopathy. Cortical vision loss was associated invariably with T2/FLAIR MRI hyperintensities in the parieto-occipital region.

Case Report: An Unusual Case of Subacute Sclerosing Panencephalitis with Distinctive Clinical and Neuroimaging Features.

Subacute sclerosing panencephalitis (SSPE) is a relentlessly progressive brain disorder with invariable mortality. Subacute sclerosing panencephalitis is common in measles-endemic areas. We report an unusual SSPE patient with distinctive clinical and neuroimaging features. A 9-year-old boy came with a 5-month history of spontaneously dropping objects from both hands. Subsequently, he developed mental decline, a loss of interest in his surroundings, decreased verbal output, and inappropriate crying and laughing along with generalized periodic myoclonus. On examination, the child was akinetic mute. The child demonstrated intermittent generalized axial dystonic storm with flexion of upper limbs, an extension of lower limbs, and opisthotonos. Dystonic posturing was more dominant on the right side. Electroencephalography revealed periodic discharges. Cerebrospinal fluid antimeasles IgG antibody titer was markedly elevated. Magnetic resonance imaging revealed marked diffuse cerebral atrophy, and periventricular T2/fluid-attenuated inversion recovery hyperintensity. T2/fluid-attenuated inversion recovery images also revealed multiple cystic lesions present in the region of periventricular white matter. The patient was given a monthly injection of intrathecal interferon-α. The patient is currently continuing in the akinetic-mute stage. In conclusion, in this report, we described an unusual case of acute fulminant SSPE in which neuroimaging demonstrated unusual multiple small discrete cystic lesions in the cortical white matter. The pathological nature of these cystic lesions currently is not clear and needs to be explored.

Dissociations in white matter tracts and neuropsychological findings in a 17 years old patient with Subacute sclerosing panencephalitis.

The present multimodal diffusion tensor imaging and neuropsychological study investigated the integrity of the white matter fascicles in a 17 years-old patient diagnosed with subacute sclerosing panencephalitis (SSPE). A brief neuropsychological testing showed that word and pseudoword repetition, naming, semantic and phonological fluency, long-term memory, working memory were impaired. A review of the literature on Diffusion weighted imaging (DWI) and Diffusion Tensor Imaging (DTI) evidenced that, studies investigating the integrity of white matter in this condition being a rare disease, are very few. Significant differences (p < 0.05) were found between the fractional anisotropy (FA) values of the controls and the patient in the Superior Longitudinal fasciculus, the Inferior Longitudinal Fasciculus, the Inferior Fronto-Occipital Fasciculus, the Uncinate Fasciculus, and the Arcuate Fasciculus with lower values in the patient. No differences were found for the corticospinal tract. The number of streamlines was significantly lower in the patient, compared to controls, for the left Superior Longitudinal fasciculus, and for the left Uncinate fasciculus while for all the other fascicles, the number did not significantly differ from controls. DTI results were consistent with the patient's cognitive profile showing impairments at repetition, at tasks tapping lexical-semantics and long-term memory / retrieval. Diffusion tensor imaging results indicate that there were diffuse alterations of the degree of anisotropic diffusion along the white matter tracts distributed in posterior-anterior direction. Differently, a selective sparing of this measure was observed along the white matter tract distributed in inferior-superior direction (the corticospinal fascicle).

Cortical activation and motor body representations in a patient with subacute sclerosing panencephalitis.

The current neuroimaging study investigated the sensorimotor maps during hand, feet and lips movements at one year after diagnosis of of subacute sclerosing panencephalitis (SSPE) in a 17 years-old patient. A lesion prediction algorithm showed that the posterior thalamic radiations, the splenium of the corpus callosum, the posterior and superior corona radiate, and the cingolum, showed a high lesion probability. Comparing the fMRI activations of the left and right hemisphere, we found that the representation of the left hand movement was more inferior/anterior and less represented than the representation of the right one; and the representation of the right foot movement was more superior, less represented than the representation of the left one and poorly activated at the predefined statistical threshold. The fMRI results are in line with the clinical report, describing an asymmetrical distribution of the periodic stereotyped myoclonic jerks, which mainly occurred for the left arm/hand and for the right leg/foot. This is the first fMRI study investigating the representation of the body parts in patients with SSPE. Results show that in SSPE the hyper-stimulation of the motor system (dedicated to the arm/hand and leg/foot more involved by the occurrence of the jerks) is accompanied by an under-activation of the corresponding motor representations in coincidence with voluntary movements.

Subacute Sclerosing Panencephalitis: Restricted Diffusion and Clinical Evolution.

Background: Subacute sclerosing panencephalitis (SSPE) is a rare entity characterized by a protracted course and progressive neurological deterioration. Objective: We present patterns of diffusion restriction in eight cases of SSPE, a seldom described imaging attribute. Methods: A retrospective analysis was performed on the clinical and neuroimaging data obtained from records of patients with proven SSPE. Patients whose magnetic resonance imaging (MRI) showed evidence of diffusion restriction were included in the analysis. MRI was performed on 3 T and 1.5-T clinical MR systems. Imaging characteristics were reviewed and tabulated by two neuroradiologists. Results: Eight SSPE patients (seven men, one woman; age range: 5-15 years; mean age: 11 years) diagnosed and managed at our institute were included in the analysis. Restricted diffusion was evident in the basal ganglia (n = 3), corpus callosum (n = 2), white matter (n = 2) and in bilateral middle cerebellar peduncles (MCP) (n = 2). One patient had diffusion restriction in the genu of the corpus callosum and bilateral frontal cortical white matter. None of the diffusion-restricted lesions showed contrast enhancement or susceptibility. Six cases fulfilled the diagnostic criteria for fulminant SSPE (fSSPE). The extent of neuroparenchymal involvement was greater in this subset of patients. Conclusions: Restricted diffusion in SSPE, hitherto infrequently described, can indeed occur in both grey and white matter structures and in both supratentorial and infratentorial compartments. Parenchymal diffusion restriction in SSPE possibly reflects an early time point in the clinical evolution. A greater extent of parenchymal diffusion restriction may portend a rapid downhill course, possibly qualifying for fSSPE.

Favorable outcomes of interferon-α and ribavirin treatment for a male with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a slow virus infection associated with mutant measles virus (MeV). The long-term outcome of antiviral treatments remains to be determined. We herein present a Japanese boy who was diagnosed with SSPE at 10 years of age. Intraventricular infusions of interferon-α effectively prevented the progress of symptoms during 14 years of follow-up period. Flow-cytometric analysis demonstrated higher proportion of T helper 17 cells (Th17, 18.2%) than healthy controls (4.8-14.5%) despite the normal subpopulation of peripheral lymphocytes. These data suggest that a group of patients with SSPE may show favorable responses to intraventricular infusions of interferon-α.

Seizures as onset symptoms and rapid course in preschool children with subacute sclerosing panencephalitis.

BACKGROUND: The clinical features and outcomes of subacute sclerosing panencephalitis (SSPE) in younger children are different from those of adults, leading easily to misdiagnosis during the early stage. So far, there are limited data related to SSPE in preschool children. METHODS: In order to summarize the clinical data and evolution of SSPE in preschool children and to expand the phenotypes of SSPE, the medical charts of preschool patients diagnosed with SSPE were retrospectively reviewed and analyzed; the clinical outcomes of the enrolled cases were evaluated and followed up. RESULTS: Overall, we included three cases in the study. Their onset age was 5 years and 2 months, 4 years and 3 months, and 4 years and 2 months, respectively. All patients presented drop attacks or jerks as the onset symptom, and one patient had concurrent gait disturbance. Atypical periodic complexes on electroencephalography (EEG) were recorded in all patients. The brain magnetic resonance imaging (MRI) findings of two cases showed demyelinating lesions predominantly on the white matter. The neurological conditions of all cases deteriorated rapidly. Two children died at 21 months and 6 months after onset, respectively. The other case progressively developed vegetative status and akinetic mutism within 4 months. CONCLUSIONS: In younger children, the characteristic features of SSPE may be seizures and gait instability as onset manifestations, atypical periodic complexes on EEG, and rapid worsening of neurological conditions.

Magnetic resonance imaging patterns of subacute sclerosing panencephalitis may mimic metabolic disorders: clinical, electroencephalographic and imaging features of six cases.

Subacute sclerosing panencephalitis is a rare, devastating neurodegenerative encephalitis whose diagnosis and therapy are still in question. Atypical clinical presentation and heterogeneity of neuroimaging findings that have been initially confused with metabolic disorders have hampered early diagnosis. To describe a series of patients with subacute sclerosing panencephalitis with imaging findings mimicking metabolic disorders. A total of six patients with subacute sclerosing panencephalitis were diagnosed from January 2012 to December 2016 in whom a metabolic disorder was suspected on initial clinical and MRI findings. Detailed laboratory investigation was performed in all patients. All patients presented with atypical neurologic manifestations, including dystonia, syncopal attacks, involuntary limb movements, meaningless speech and ataxia. Magnetic resonance imaging abnormalities included bilateral putaminal, bilateral posterior periventricular white matter and diffuse or splenial corpus callosum involvement which are particularly unusual in SSPE and mostly observed in metabolic disorders. All patients had elevated cerebrospinal fluid Ig G measles antibodies. The diagnosis of subacute sclerosing panencephalitis through clinical and imaging features can be considerably challenging. It is crucial to differentiate it from metabolic disorders, since the management and clinical outcome are different.

Neuropathological Alzheimer's Disease Lesions in Nasu-Hakola Disease with TREM2 Mutation: Atypical Distribution of Neurofibrillary Changes.

Nasu-Hakola disease is a rare autosomal recessive disorder associated to mutations in TREM2 and DAP12 genes, neuropathologically characterized by leukoencephalopathy with axonal spheroids. We report the neuropathologic findings of a 51-year-old female with a homozygous mutation (Q33X) of TREM2 gene. Beside severe cerebral atrophy and hallmarks of Nasu-Hakola disease, significant Alzheimer's disease lesions were present. Neurofibrillary changes showed an atypical topographic distribution being severe at spots in the neocortex while sparing the mesial temporal structures. Our finding suggests that TREM2 genetic defects may favor Alzheimer's disease pathology with neurofibrillary changes not following the hierarchical staging of cortical involvement identified by Braak.

Clinical conundrum: status epilepticus culminating into acute dystonia myoclonus.

A 7-year-old child who suffered from symptomatic focal epilepsy as a sequel to perinatal hypoxia used to have frequent seizures. This time she developed prolonged status epilepticus lasting for over 5 hours. She received a treatment in the form of intravenous midazolam and reinitiation of sodium valproate and clobazam that were discontinued previously. Seizures were controlled over a couple of hours, but she remained unresponsive. Later, she developed acute onset dystonia (day 3 post-status epilepticus) and also myoclonic jerks. She presented to us after 3 weeks of onset of these complaints and we considered hypoxic encephalopathy resulting from prolonged status epilepticus or acute encephalitis or non-convulsive status epilepticus. However, acute onset dystonia and periodicity of myoclonic jerks were pointers against it, and on evaluation, she was diagnosed with atypical fulminant subacute sclerosing panencephalitis (SSPE). Knowing the atypical presentations of SSPE is important in planning management and prognostication.

Subacute Sclerosing Panencephalitis Causing Rapidly Progressive Dementia and Myoclonic Jerks in a Sexagenarian Woman.

Background: Subacute sclerosing panencephalitis (SSPE) is a disease of childhood and adolescence, but can affect adults. Rapidly progressive cognitive decline, seizures including myoclonic jerks, spasticity, ataxia, visual disturbances, and incontinence are typical manifestations. Case report: A 62-year-old woman who presented with rapidly progressive dementia and myoclonus was diagnosed with SSPE. There was resolution of the movement disorder with clonazepam and valproic acid treatment and some amelioration of cognitive decline after 3 months of therapy with interferon alfa and isoprinosine. Discussion: With the recent rise in measles cases worldwide, any increased incidence of SSPE would require vigilance for early interventions.