J. Moshe Gomori

Extracranial carotid artery stenting followed by intracranial stent-based thrombectomy for acute tandem occlusive disease

Objective Acute tandem occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. We describe our experience with emergency stent-assisted ICA angioplasty and intracranial stent-based thrombectomy of tandem occlusions. Methods Procedures were performed from March 2010 to December 2013. National Institutes of Health Stroke Score (NIHSS) and Alberta Stroke Program Early CT Score (ASPECTS), occlusion sites, collateral supply, procedural details, and outcomes were retrospectively reviewed with IRB waiver of informed consent. Results 24 patients, mean age 66 years, mean admission NIHSS 20.4, and mean ASPECTS 9 were included. Occlusion sites were proximal ICA–middle cerebral artery (MCA) trunk in 17 patients, proximal ICA–ICA terminus in six, and ICA–MCA–anterior cerebral artery in one. Stent-assisted cervical ICA recanalization was achieved in all patients, with unprotected pre-angioplasty in 24/24, unprotected stenting in 16/24 (67%), and protected stenting in 8/24 (33%), followed by stent-thrombectomy in 25 intracranial occlusions. There was complete recanalization/complete perfusion in 19/24 (79%), complete recanalization/partial perfusion in 3/24 (13%), and partial recanalization/partial perfusion in 2/24 (8%) with no procedural morbidity/mortality. Mean time to therapy was 3.8 h (range 2–5.5) and mean time to recanalization was 51 min (range 38–69). At 3-month follow-up, among 17/22 surviving patients (77%), 13/17 (76%) were modified Rankin Scale (mRS) 0–2 and 3/17 (18%) were mRS 3. Conclusions In acute tandem ICA–MCA/distal ICA occlusions, extracranial stenting followed by intracranial stent-based thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted.

Intracranial meningiomas after high‐dose irradiation

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high‐dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high‐dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean, age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with “spontaneous” meningiomas. Similar to the situation with meningiomas after low‐dose irradiation, a relatively high proportion of meningiomas induced by high‐dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high‐dose radiation may play a role in the pathogenesis of meningiomas.

Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings.

Adult polyglucosan body disease (APBD) is an autosomal recessive leukodystrophy characterized by neurogenic bladder, progressive spastic gait, and peripheral neuropathy. Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency. To improve clinical diagnosis and enable future evaluation of therapeutic strategies, we conducted a multinational study of the natural history and imaging features of APBD.

Striatal degeneration and spongy myelinopathy in glutaric acidemia

The neuropathological findings in a 6 1/2-year-old boy with glutaric acidemia (GA) are described, and the pathology of 7 additional literature cases is briefly reviewed. Bilateral striatal degeneration and spongy change of the white matter were the salient features in this case and seem to represent the cardinal pathological features of the disease. Spongy myelinopathy was the result of intramyelinic vacuolation due to splitting of the myelin sheath along the intraperiod line, as illustrated here for the first time in GA. Based on morphological, biochemical and pharmacological data from humans and experimental animals, it is hypothesized that excitotoxin-mediated neuronal damage may account for the striatal degeneration, while toxic effect on myelin metabolism by the metabolic derangement of GA may explain the widespread white matter changes.

A hyperpolarized choline molecular probe for monitoring acetylcholine synthesis

Choline as a reporter molecule has been investigated by in vivo magnetic resonance for almost three decades. Accumulation of choline metabolites (mainly the phosphorylated forms) had been observed in malignancy in preclinical models, ex-vivo, in vivo and in patients. The combined choline metabolite signal appears in (1) H-MRS of the brain and its relative intensity had been used as a diagnostic factor in various conditions. The advent of spin hyperpolarization methods for in vivo use has raised interest in the ability to follow the physiological metabolism of choline into acetylcholine in the brain. Here we present a stable-isotope labeled choline analog, [1,1,2,2-D(4) ,2-(13) C]choline chloride, that is suitable for this purpose. In this analog, the (13) C position showed 24% polarization in the liquid state, following DNP hyperpolarization. This nucleus also showed a long T(1) (35 s) at 11.8 T and 25 °C, which is a prerequisite for hyperpolarized studies. The chemical shift of this (13) C position differentiates choline and acetylcholine from each other and from the other water-soluble choline metabolites, namely phosphocholine and betaine. Enzymatic studies using an acetyltransferase enzyme showed the synthesis of the deuterated-acetylcholine form at thermal equilibrium conditions and in a hyperpolarized state. Analysis using a comprehensive model showed that the T(1) of the formed hyperpolarized [1,1,2,2-D(4) ,2-(13) C]acetylcholine was 34 s at 14.1 T and 37 °C. We conclude that [1,1,2,2-D(4) ,2-(13) C]choline chloride is a promising new molecular probe for hyperpolarized metabolic studies and discuss the factors related to its possible use in vivo.

Pharmacokinetics of methotrexate in cerebrospinal fluid and serum after osmotic blood‐brain barrier disruption in patients with brain lymphoma

To evaluate the pharmacokinetics of methotrexate in ventricular cerebrospinal fluid and serum after osmotic blood‐brain barrier disruption and intra‐arterial administration compared with intravenous or simple intra‐arterial infusion in patients with primary central nervous system lymphoma.

In vivo magnetic resonance imaging of glucose - initial experience.

A new noninvasive, nonradioactive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog labeled with (13)C at all six positions increased the overall hyperpolarized imaging signal; deuteration at all seven directly bonded proton positions prolonged the spin-lattice relaxation time. High-bandwidth (13)C imaging overcame the large glucose carbon chemical shift dispersion. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8 s after the start of bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12 and 20 s. The heart-to-vasculature intensity ratio at 20 s suggests myocardial uptake. Cancer imaging, currently performed with (18)F-deoxyglucose positron emission tomography (FDG-PET), warrants further investigation, and glucose imaging could be useful in a vast range of clinical conditions and research fields where the radiation associated with the FDG-PET examination limits its use.

Gliomas following low-dose irradiation to the head report of three cases

Three patients developed cerebral gliomas decades after exposure to low-dose x-ray irradiation in childhood for the treatment of tinea capitis. One of the patients had a glioblastoma multiforme concomitant with multiple intracranial meningiomas, a condition highly correlated with previous irradiation. The other tumors were malignant cerebellar astrocytoma and a diffuse cerebral astrocytoma. We review the evidence suggesting that low-dose irradiation is involved in the pathogenesis of gliomas.

Reversible functional connectivity disturbances during transient global amnesia.

Transient global amnesia (TGA), an abrupt occurrence of severe anterograde episodic amnesia accompanied by repetitive questioning, has been known for more than 50 years. Despite extensive research, there is no clear evidence for the underlying pathophysiological basis of TGA. Moreover, there is no neuroimaging method to evaluate TGA in real time.

In vitro visualization of betaine aldehyde synthesis and oxidation using hyperpolarized magnetic resonance spectroscopy

Real-time monitoring of betaine aldehyde metabolism at high temporal resolution was accomplished using a hyperpolarized choline analog and (13)C-NMR. This represents the first observation of an aldehyde intermediate on hyperpolarized MR and opens the way for kinetic studies of oxidase/dehydrogenase enzymes in vitro and in vivo.