Epilepsia partialis continua revealing idelalisib-associated PML-IRIS: clinical and pathological features.

Idelalisib, a selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, is a newly approved second-line drug for patients with chronic lymphocytic leukemia. Recent clinical trials have suggested a possible association between idelalisib treatment and development of progressive multifocal leukoencephalopathy (PML) due to John Cunningham virus (JCV) reactivation. Nevertheless, clinical course and radiological and pathological features of idelalisib-induced PML still need to be clarified. We provide here the first clinicopathological description of idelalisib-associated PML in a patient who developed epilepsia partialis continua (EPC) as the first manifestation of the disease. Since EPC could present without electroencephalogram alterations, it is crucial to recognize the clinical features of this epileptic condition. EPC is characterized by the presence of repetitive, irregular, clonic jerking, often associated with hemiparesis and involvement of distal rather than proximal muscle groups. Moreover, we highlight the importance of brain biopsy in selected cases when there is a high clinical suspicion of PML, despite negative JCV testing in the cerebrospinal fluid. The pathological finding of prominent inflammatory infiltrate observed here was consistent with a diagnosis of immune reconstitution inflammatory syndrome (IRIS). IRIS is often associated with PML as a paradoxical worsening of clinical symptoms due to an overreacting immune response, in the context of previous immunosuppression. The unprecedented pathologic observation of IRIS in idelalisib-associated PML provides further insights into the pathogenesis of this rare neurological side effect.

Epilepsia partialis continua following a Western variant tick-borne encephalitis.

Epilepsia partialis continua (EPC) is a rare entity, first described in 1894 by Kozevnikov, as a variant of simple focal motor status epilepticus. EPC is most frequently characterized by motor symptoms, but as recently described, non-motor manifestations may occur, such as somatosensory symptoms or aura continua. EPC in adults has been attributed to various etiologies: infectious, vascular, neoplastic, and metabolic. According to the recent definition, we reported a case of EPC with behavioral symptoms, following a tick-borne encephalitis (TBE) contracted in an endemic area (North Eastern Italy). Patient's symptom was a poorly localized "whole body sensation", which is reported as a condition occurring only in frontal lobe epilepsy. Patient's EEG showed a left frontal predominance of epileptiform discharges. Literature highlighted the importance of the Far-eastern TBE variant as a cause of EPC, since no Western variant TBE cases are reported. In contrast to what was claimed so far, our case demonstrates that not only the Far-eastern TBE variant, but also Western variant TBE is a cause of EPC. Prognosis of EPC depends largely on the underlying etiology, and it is frequently drug-resistant. Our patient was treated with intravenous levetiracetam, with a subsequent clinical recovery and a disappearance of epileptiform discharges. The rapid clinic and electroencephalographic response to levetiracetam confirm that it can be a promising therapeutic option for treatment of EPC.

Diaschisis in chronic viral encephalitis with Koshevnikov syndrome.

The authors report a 61-year-old man with chronic viral encephalitis and Koshevnikov syndrome occurring 42 months after initial symptom of right hemiparesis. Serial computed tomography of the brain showed changes in the attenuation of the left temporal lobe lesion over time. Magnetic resonance images of the brain showed enlargement of left temporoparietooccipital lobes with cortical gyral enhancement on T1-weighted images following intravenous administration of gadolinium-DTPA. 99mTc-HMPAO single-photon emission computerized tomography showed increased radioactivity and hyperperfusion in the left temporoparietal region with paradoxically decreased local tissue perfusion at the contralateral right hemisphere. Follow-up magnetic resonance images of the brain 4 years later showed atrophy of bilateral cerebral hemispheres. We postulate that a "transcallosal diaschisis" with subsequent degeneration is a possible mechanism. A brain biopsy from the left temporal lobe lesion showed pictures compatible with viral encephalitis probably herpes simplex encephalitis.

Rasmussen's syndrome: a study of potential viral etiology.

Rasmussen's syndrome (RS) is a devastating constellation of severe, unilateral focal motor epilepsy resistant to anticonvulsant therapy, followed by ipsilateral neurological deficits and neuropathological evidence of a chronic encephalitis occurring primarily in the pediatric population. Recent reports have identified viral genomic material for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) using in situ hybridization (ISH) in brain tissue of RS patients. We studied 10 biopsy- and resection-specimens from seven patients using biotinylated double-stranded DNA probes to CMV, herpes simplex virus (HSV) and EBV to confirm these results. Two patient samples were also evaluated by electron microscopy and one using standard immunoperoxidase techniques. We were unable to identify any evidence of viral material utilizing one of these techniques. There was some nonspecific localization of crystalline material by in situ hybridization over nuclei, which may account for literature reports of positivity, although one cannot be sure since photomicrographs were not included in these reports. Although the neuropathological morphology of the identifiable lesions in resected specimens is consistent with that seen in other viral encephalitides, our findings fail to support the role of CMV, HSV, or EBV as the etiology and sole factor in the development of Rasmussen's syndrome.