Guiyun Wu

Homozygous mutation in SAMHD1 gene causes cerebral vasculopathy and early onset stroke

We describe an autosomal recessive condition characterized with cerebral vasculopathy and early onset of stroke in 14 individuals in Old Order Amish. The phenotype of the condition was highly heterogeneous, ranging from severe developmental disability to normal schooling. Cerebral vasculopathy was a major hallmark of the condition with a common theme of multifocal stenoses and aneurysms in large arteries, accompanied by chronic ischemic changes, moyamoya morphology, and evidence of prior acute infarction and hemorrhage. Early signs of the disease included mild intrauterine growth restriction, infantile hypotonia, and irritability, followed by failure to thrive and short stature. Acrocyanosis, Raynaud’s phenomenon, chilblain lesions, low-pitch hoarse voice, glaucoma, migraine headache, and arthritis were frequently observed. The early onset or recurrence of strokes secondary to cerebral vasculopathy seems to always be associated with poor outcomes. The elevated erythrocyte sedimentation rate (ESR), IgG, neopterin, and TNF-α found in these patients suggested an immune disorder. Through genomewide homozygosity mapping, we localized the disease gene to chromosome (Chr) 20q11.22-q12. Candidate gene sequencing identified a homozygous mutation, c.1411–2A > G, in the SAMHD1 gene, being associated with this condition. The mutation appeared at the splice-acceptor site of intron 12, resulted in the skipping of exon 13, and gave rise to an aberrant protein with in-frame deletion of 31 amino acids. Immunoblotting analysis showed lack of mutant SAMHD1 protein expression in affected cell lines. The function of SAMHD1 remains unclear, but the inflammatory vasculopathies of the brain found in the patients with SAMHD1 mutation indicate its important roles in immunoregulation and cerebral vascular hemeostasis.

Optimizing SPECT SISCOM analysis to localize seizure‐onset zone by using varying z scores

Subtraction ictal single photon emission computed tomography (SPECT) co‐registered to magnetic resonance imaging (MRI) (SISCOM) is a useful modality to identify epileptogenic focus. Using this technique, several studies have generally considered the area of highest ictal hyperperfusion, as outlined by thresholding the difference images with a standard z score of 2, to be highly concordant to the epileptogenic focus. In clinical practice, several factors influence ictal hyperperfusion and using different SISCOM thresholds can be helpful. We aimed to systematically evaluate the localizing value of various z scores (1, 1.5, 2, and 2.5) in a seizure‐free cohort following resective epilepsy surgery, and to examine the localizing information of perfusion patterns observed at each z score.

Multiple auras Clinical significance and pathophysiology

Background: Patients with partial epilepsy may report multiple types of aura during their seizures. The significance of the occurrence of multiple auras in the same patient is not known. Methods: The clinical and electrophysiologic characteristics of patients with more than one aura type (abdominal, auditory, autonomic, gustatory, olfactory, psychic, somatosensory, and visual auras), evaluated in the Cleveland Clinic epilepsy monitoring unit between 1989 and 2005, were studied. Results: Thirty-one patients experienced multiple aura types during a seizure. Ninety percent of patients with at least two aura types (n = 31) and 100% percent of patients with at least three aura types (n = 12) had seizures arising from the right/nondominant hemisphere. EEG seizures remained restricted in all patients during their auras. Twenty patients had epilepsy surgery with seizure freedom in 53%. Subdural EEG recordings in six patients showed either a march of sequential auras, or in one case, several ictal onset zones resulting in separate isolated auras. Ictal SPECT in six patients with right-sided seizures showed a lack of activation in brainstem structures. Conclusions: Most patients who report multiple aura types have localized epilepsy in the nondominant hemisphere, and are good surgical candidates. A common mechanism for multiple auras may be a spreading but restricted EEG seizure activating sequential symptomatogenic zones, but without the ictal activation of deeper structures or contralateral spread to cause loss of awareness and amnesia for the auras.

Radiological Correlate of Ocular Flutter in a Case with Paraneoplastic Encephalitis

We present an interesting [18F]fluoro‐2‐deoxyglucose positron emission tomography (FDG‐PET) imaging finding in a patient with ocular flutter and cerebellar ataxia as part of anti‐Ma 1/2 antibody‐mediated paraneoplastic syndrome associated with a testicular seminoma. He had a typical anterior mesial temporal hyperintensity on magnetic resonance imaging (MRI) without gadolinium enhancement. In addition, his FDG‐PET images showed increased deep cerebellar and inferior rectus and superior oblique ocular muscles FDG uptake. This case is the first to visualize in vivo the possible underlying neuropathological mechanism of ocular flutter associated with cerebellar nuclei on functional imaging.

Ictal single photon emission computed tomography in epileptic auras

Little is known about whether ictal single photon emission computed tomography (SPECT) during an isolated aura can localize the epileptogenic zone (EZ). This study seeks to evaluate the yield of ictal SPECT injection in isolated epileptic auras.

Subcortical SISCOM hyperperfusion: Should we pay more attention to it?

PURPOSE Demonstrating cerebral blood flow changes during seizures, ictal-interictal single photon emission computed tomography (SPECT) with co-registration to MRI (SISCOM) reflects brain activation and its pathways of spread. To investigate subcortical ictal hyperperfusion patterns during focal seizures, we retrospectively reviewed SISCOM analysis of patients who became seizure-free after cortical resection. Our aim was to evaluate the relationship between epileptogenic zones and subcortical hyperperfusion. METHOD 67 patients were identified as having SISCOM evaluation and having remained seizure-free for at least one year after surgical resection. SISCOM analysis was blindly reviewed for localization of basal ganglia (BG), thalamic (TN) and cerebellar (CH) hyperperfusion based on three different thresholds. Subcortical activation and epilepsy characteristics were then compared between patients. For a given region of interest and threshold, the sensitivity, specificity and positive and negative predictive value for correct lateralization of the epilepsy side was calculated. RESULTS Depending on the threshold used, BG hyperperfusion was found in 37.3-73.9% of patients, TN hyperperfusion in 31.3-68.1% and CH hyperperfusion in 13.5-29%. For a threshold of 1.5, the best predictive positive value for correct lateralization of the epilepsy side was obtained with BG/CH coactivation (89%). For a threshold of 2.0 and 2.5, it was obtained with BG/TN coactivation (88%) and BG activation (82%), respectively. CONCLUSION Subcortical SISCOM hyperperfusion could offer additional clues in terms of lateralization.

Quantitative positron emission tomography-guided magnetic resonance imaging postprocessing in magnetic resonance imaging-negative epilepsies.

Detection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD.