A Japanese case with Nasu-Hakola disease of DAP12 gene mutation exhibiting precuneus hypoperfusion.

A 38-year-old Japanese man with Nasu-Hakola disease (NHD) had repeated pathological fractures and frontal lobe symptoms which developed when he was 18 and 26 years old, respectively. Neuropsychological testing showed memory impairment, and in particular, visuo-spatial memory at the age of 35. Furthermore, single-photon emission computed tomography revealed precuneus hypoperfusion. The patient later suffered prolonged convulsive seizures, which left him in a persistent vegetative state. Genetic testing confirmed a heterozygous mutation in the DAP12 gene (a single-base deletion of 141 G in exon 3) specific to NHD. Precuneus dysfunction might contribute to characteristic memory impairment of NHD.

Serial diffusion-weighted imaging in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis may be associated with clinical features of frontal lobe dysfunction. We previously reported that frontal lobe volume falls significantly as clinical stage progresses, using three-dimensional magnetic resonance imaging-based brain volumetry. The hypothesis that frontal volume increases correlate with clinical improvement, however, was not tested in our previous study. Therefore, we reevaluated our patient with subacute sclerosing panencephalitis, to determine whether apparent diffusion coefficient maps can characterize the clinical course of subacute sclerosing panencephalitis. We studied an 8-year-old boy with subacute sclerosing panencephalitis, using serial diffusion-weighted imaging magnetic resonance imaging, and measured the regional apparent diffusion coefficient. The regional apparent diffusion coefficient of the frontal lobe decreased significantly with clinical progression, whereas it increased to within normal range during clinical improvements. The apparent diffusion coefficient of the other regions did not change. These results suggest that the clinical signs of patients with subacute sclerosing panencephalitis are attributable to frontal lobe dysfunction, and that apparent diffusion coefficient measurements may be useful in predicting the clinical course of subacute sclerosing panencephalitis.

Pharmacokinetics and effects of ribavirin following intraventricular administration for treatment of subacute sclerosing panencephalitis.

Ribavirin is a broad-spectrum antiviral drug with inhibitory activity against many RNA viruses, including measles virus. Five patients with subacute sclerosing panencephalitis (SSPE) were treated with ribavirin by intraventricular administration. Although there were transient side effects attributed to ribavirin, such as drowsiness, headache, lip and gingival swelling, and conjunctival hyperemia, intraventricular ribavirin therapy was generally safe and well tolerated. The cerebrospinal fluid (CSF) ribavirin concentration decreased, as described by a monoexponential function, after a single intraventricular dose. There was considerable interindividual variability, however, in the peak level and half-life. We aimed to adjust the individual dose and frequency of intraventricular administration based on the peak level and half-life of ribavirin in the CSF in order to maintain the CSF ribavirin concentration at the target level. Clinical effectiveness (significant neurologic improvement and/or a significant decrease in titers of hemagglutination inhibition antibodies against measles virus in CSF) was observed for four of five patients. For these four patients, CSF ribavirin concentrations were maintained at a level at which SSPE virus replication was almost completely inhibited in vitro and in vivo, whereas the concentration was lower in the patient without clinical improvement. These results suggest that intraventricular administration of ribavirin is effective against SSPE if the CSF ribavirin concentration is maintained at a high level. Intraventricular ribavirin therapy should be pursued further for its potential use for patients with SSPE and might be applied in the treatment of patients with encephalitis caused by other RNA viruses.

[Subacute sclerosing panencephalitis (SSPE) as differential diagnosis in severe personality changes and ataxia--case report and literature review]. / Subakute, sklerosierende Panenzephalitis (SSPE) als Differentialdiagnose einer schweren Wesensveränderung und Ataxie--Fallbericht und Literaturüberblick.

An 8 year old girl presented with progressive change of personality and spastic ataxia since 4 weeks. A year before she had developed focal grand-mal-seizures; at this time laboratory and radiologic findings were normal. The EEG on admission demonstrated marked changes with partially focal, partially generalized hypersynchronic activity, but no SSPE-typical Radermecker-complexes. There were no cells in the cerebrospinal fluid (CSF), a slightly increased level of protein and a normal glucose. Isoelectric focusing showed predominantly measles-specific oligoclonal IgG bands in the CSF. In the magnetic resonance tomography multiple focal white matter lesions in the basal ganglia as well as in cortical and occipitoparietal regions could be seen. At the age of two the girl had suffered from measles, the child didn't receive any vaccination. The combination of history, CSF-, MRI-results and EEG lead to the diagnosis of subacute sclerosing panencephalitis (SSPE). After 3 months the clinical and radiological abnormalities had markedly increased. On the background of this history SSPE should be considered as differential diagnosis in patients with changes of personality.

Subacute sclerosing panencephalitis presenting with psychosis and possible sexual abuse.

A previously healthy 8-year-old girl began to experience nightmares, soon followed by sleeplessness and perceptual abnormalities including visual hallucinations. She also complained that she had been attacked and possibly assaulted sexually. Physical investigations were considered to have provided no relevant abnormality and psychiatric enquiries were begun directed towards possible sexual abuse. However, the child's mental and physical state continued to deteriorate and evidence of a progressive organic process was then obtained from past school reports, review of the initial EEG findings and further EEG investigations. The latter in particular indicated a diagnosis of SSPE which was confirmed immunologically. Treatment was ineffective and the child died 7 months after the onset of the illness. The details of the psychological changes at the onset of SSPE are ill-defined. This case illustrates that they can include psychotic phenomena but also that the basic nature of the disorder may be misconstrued as psychological depending on the circumstances.

Use of a brief assessment examination in a study of subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a degenerative disease affecting children and young adults that remains a distinct and relatively frequent problem in developing countries worldwide. Recent advances in treatment prompted a study at King Faisal Specialist Hospital, Riyadh, Saudi Arabia, using oral isoprinosine and intraventricular alpha-interferon. Initially, the Neurological Disability Assessment and Index was used for tracking patient progress. However, an additional means of assessment was deemed necessary and the Brief Assessment Examination was devised. Largely cognitive based, the Brief Assessment Examination appeared to be more sensitive to mental status changes than the Neurological Disability Assessment and Index, though it correlated modestly with the Neurologic Disability Assessment and Index and more strongly with staging. In addition, the Brief Assessment Examination can be administered by technician-level staff with a minimum of training. Though more study is needed, preliminary findings suggest that the Brief Assessment Examination should be a useful tracking tool for subacute sclerosing panencephalitis, particularly in the developing world.

[Changes of cognitive and emotional processes during immunostimulatory treatment in subacute sclerosing panencephalitis]. / Zmiany w zakresie procesów poznawczych i emocjonalnych podczas leczenia immunostymulujacego chorych z podostrym stwardniajacym zapaleniem mózgu (SSPE).

In 35 cases of SSPE sensibilized neuropsychological testing was done before and after 6 months of immunostimulatory and virostatic treatment. Three groups of patients were studied. All groups received isoprinosine, one group was given additionally TFX-thymus extract Polfa, and another group received additionally Propionibacterium granulosum KP-45. A tendency for improvement of verbal function and emotional status was observed only in the group receiving isoprinosine with propionibacterium. In both remaining groups, receiving only isoprinosine or isoprinosine with TFX worsening was noted, particularly in the isoprinosine-only group. This was particularly evident in the visuospatial orientation. Prolongation of survival time in SSPE owing to specific treatment increases the need for psychoreactive and therapeutic influences for stimulation of cognitive processes.

[A personal case report of subacute sclerosing panencephalitis in an adult]. / Contributo personale alla panencefalite sclerosante subacuta nell'adulto.

The paper describes the case of a 37-year woman, with no past history of measles infection, who initially showed behavioral disorders, interpretative and reference deliria with a persecutory content. Extrapyramidal rigidity, bradykinesia, myoclonia, dementia, hyperpyrexia and coma with decerebrate rigidity subsequently appeared. Instrumental tests showed a spinal fluid status with intrathecal IgG synthesis and oligoclonal pattern, aspecific signs of widespread electric anomalies in the EEG. Encephalic CT and NRM were altered showing multifocal damage to the white substance. Anti-measles antibody titres were high in both spinal fluid and serum. Post-mortem histological tests confirmed the clinical hypothesis of subacute sclerosing panencephalitis. The paper reviews existing reports and pays special attention to cases of SSPE in adults and those cases with a psychiatric outcome. Lastly, the role of neuroradiological methods in the diagnostic iter is assessed.

Subacute sclerosing panencephalitis presenting as schizophreniform psychosis.

A case of 21-year-old woman with subacute sclerosing panencephalitis presenting with paranoid schizophreniform symptoms is presented. The relationship between viral encephalitis and psychiatric symptoms is briefly considered.

Subacute sclerosing panencephalitis (SSPE) presenting at the age of 21 as a schizophrenia-like state with bizarre dysmorphophobic features.

A case is described of a 21-year-old man who, after extensive investigations by the general physicians and neurologists, was transferred to a psychiatric hospital with a diagnosis of functional illness. The clinical picture at that stage simulated schizophrenia with prominent dysmorphophobic features. A diagnosis of subacute sclerosing panencephalitis was then made 9 months after the onset.

[Long-term subacute sclerosing panencephalitis with sensorial transcortical aphasia. Description of a case]. / Panencefalite sclerosante subacuta (PESS) a lunga sopravvivenza con afasia transcorticale sensoriale. Descrizione di un caso.

A 16 year boy with subacute sclerosing panencephalitis in stage 4 is described. Neuropsychological analysis reveal a transcortical sensorial aphasia. Behavior therapies of shaping and fading are proposed.

The variable natural history of subacute sclerosing panencephalitis: a study of 118 cases from the Middle East.

A variable natural history was found in a standardized follow-up study of 118 patients with subacute sclerosing panencephalitis (SSPE). Only 20% followed the sequence:behavior change, mental deterioration, periodic attacks, severe debility, and death within a year. Six stages were identified: 0, subtle psychointellectual symptoms; 1, obvious psychointellectual and neurological changes; 2, stereotyped attacks; 3, vegetative psychomotor condition; 4, improvement; 5, relapse. Illness began in stage 0 for 32%; 1, 36%; 2, 19%; 1 and 2 simultaneously, 13%. In early development, 77% were hyperactive, and 27% had psychointellectual difficulties one to five years prior to obvious illness. The average duration of each stage was as follows: stage 0, two years; 1, 2.5 months; 2, 7.5 months; 3, 5.5 months; 4, 3.5 years; 5, 1.5 years. Noteworthy improvements and plateaus occurred in more than half of the patients. In stage 4, improvement was long-term and substantial for 5% and modest for 18%. Survival followed an exponential curve with an average half-life of 1.8 years; 41% of the patients survived beyond two years. Half of the patients passed through neither stage 0 nor stage 4; their half-life was 0.7 years. The remainder had a half-life of 3.0 years.

Isoprinosine in subacute sclerosing panencephalitis.

An open therapeutic trial of isoprinosine was conducted in 15 patients with subacute sclerosing panencephalitis (SSPE). Long-term remissions occurred in 5 (33 percent), with documented improvement sustained for 2 or more years. Another patient was in remission 9 months after starting treatment, and three patients had transient remissions or stabilization. The disease was unaltered in five patients who had rapidly progressive SSPE when treatment started. These results compare with an average remission rate of about 5 percent in several series of untreated cases of SSPE or in cases treated with other antiviral agents. Patients in remission continued to have elevated cerebrospinal fluid (CSF) IgG and measles antibody titers, with one exception. Isoprinosine was tolerated for several years without side effects, except for mild hyperuricemia.