A 46-year-old Saudi male right-handed teacher was in his usual state of health until four months prior to his presentation. This was when he started to have a wide-based gait, unsteadiness as well as several attacks of staring and unresponsiveness. It was associated with lip smacking lasting a few seconds as noticed by his colleagues and students at school. The patient would occasionally complain of a holocranial headache lasting hours to days, incapacitating him from doing his duties of teaching and home commitments.
One week prior to his presentation to our institute, he started complaining of severe headache while in class. His colleagues directed him to a local hospital. On his way he developed abnormal movements with loss of consciousness in the car. The semiology of the abnormal movements reflected left-sided tonic-clonic seizures with uprolling of the eyes, urinary incontinence, frothing of saliva that lasted few minutes and was aborted spontaneously. This was followed by a state of confusion for hours.
During the admission at the local hospital, his brother witnessed some tonic posturing of the left arm for an estimated duration of 2 minutes during which the patient was unresponsive to verbal stimuli. The patient was discharged from the local hospital without anti-seizure therapy.
The patient was referred from the local hospital to our center for seizure evaluation. He presented to the Epilepsy clinic at KFSH&RC with altered consciousness and found to have aphasia. He was non-fluent, and following commands by gesture only. He was rushed to the neurophysiology clinic for an urgent electroencephalogram (EEG).
A 30-minute EEG recording revealed non-convulsive status epilepticus (NCSE). It showed a severely abnormal EEG consisting of a slow background of 6-7 Hertz (Hz) with 1-3 Hz focal slowing in the left anterior and mid temporal region. Several seizures during the recording were associated with evolution of sharp waves and spikes recurring at 3-5 Hz over the left mid and posterior temporal region. During this time the patient was unresponsive with eye blinking. This expedited his admission for investigation and management of his seizures.
He was admitted with a diagnosis of NCSE, started on intravenous (IV) phenytoin and long-term EEG monitoring. He continued to have frequent attacks of non-convulsive seizures, despite being on multiple anti-seizure drugs including lamotrigine, carbamezapine, valporic acid and pyridoxine. Long term EEG monitoring captured 13 attacks of seizures during the first 48 h. Electrographic seizure onset occurred with the onset of rhythmic sharply-contoured theta evolving to delta activity maximal in the left temporal region during unresponsiveness for 5-7 minutes.
Computed tomography (CT) brain was unremarkable for any abnormality. Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis showed an elevated protein of 747 mg/dl, and white blood cells (WBC) of 51 with 94% lymphocytes. Because the CSF analysis revealed lymphocytic pleocytosis in the presence of NCSE, the patient was started on antiviral and antibiotics for possible meningo-encephalitis. CSF viral and bacterial etiologies as well as, mycobacterium tuberculosis, syphilis, brucella and sarcoidosis were ruled out.
Brain Magnetic Resonance Imaging (MRI), Magnetic Resonance Angiography and Magnetic Resonance Venography was performed. Brain MRI revealed the presence of multi-territorial, scattered small deep white matter lesions on the fluid-attenuated inversion recovery (FLAIR) sequence involving the right corona radiate, right inferior cerebellar and cortical areas of the left parietal lobe with corresponding slight enhancement following gadolinium administration. There was no major arterial vascular occlusion, and preserved flow related enhancement of the major dural venous sinuses. The images were thought to be radiologically suggestive of inflammatory vasculitic lesions or ictal hypoxemia. (Fig. 1).
The seizures became drug-resistant despite extensive investigations and maximum therapy for 48 h with antibiotics, antiviral and the multiple anti-seizure medications. At that point, the diagnosis of NORSE was entertained.
Autoimmune encephalitis was suspected. Serum and CSF autoimmune and paraneoplastic markers were obtained and the patient was started empirically on intravenous steroids for three days. Erythrocyte sedimentation rate (ESR) was mildly elevated. Surprisingly, the patient's autoimmune workup including C-reactive protein, antinuclear antibodies, rheumatoid factor (RF), cytoplasmic anti-neutrophil cytoplasmic antibody titers and cryoglobulins were negative (Table 1, Table 2). A CT scan of the chest, abdomen and pelvis was done and revealed no abnormalities. Cerebral angiogram was done as part of the workup for CNS vasculitis and showed no evidence of small vessel disease. (Fig. 2) Despite extensive investigation no identifiable cause could be delineated.
Interestingly, his speech, gait and orientation improved dramatically returning to near normal after the intravenous pulse steroid therapy. He was discharged on oral prednisolone tapering dose, and scheduled for follow up Brain MRI 3 months from the discharge date.
On follow up, he was doing well clinically with great satisfaction in performing the daily activities independently, but still unable to return to work. His repeated brain MRI showed dramatic worsening which was attributed most probably to the tapering of corticosteroid (Fig. 3). He was readmitted for further investigation for investigation of the worsening Brain MRI. LP was repeated and showed elevated protein of 454 mg/dl and WBC of 2 cells.
Inclined to reach a diagnosis, brain biopsy was performed and the histopathology picture was suggestive of small vessel vasculitis. The biopsy was composed of many cortical and white matter fragments showing many focal angiocentric mononuclear inflammatory cell infiltrates composed almost exclusively of lymphocytes, predominantly T cells (Fig. 4). Patient was started on cyclophosphamide and showed a dramatic response to the treatment.