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Matthew F. Philips, Linda J. Bagley, Grant P. Sinson, Eric C. Raps, Steven L. Galetta, Eric L. Zager and Robert W. Hurst

Object. The authors sought to treat potentially catastrophic intracranial dural and deep cerebral venous thrombosis by using a multimodality endovascular approach.

Methods. Six patients aged 14 to 75 years presented with progressive symptoms of thrombotic intracranial venous occlusion. Five presented with neurological deficits, and one patient had a progressive and intractable headache. All six had known risk factors for venous thrombosis: inflammatory bowel disease (two patients), nephrotic syndrome (one), cancer (one), use of oral contraceptive pills (one), and puerperium (one). Four had combined dural and deep venous thrombosis, whereas clot formation was limited to the dural venous sinuses in two patients. All patients underwent diagnostic cerebral arteriograms followed by transvenous catheterization and selective sinus and deep venous microcatheterization. Urokinase was delivered at the proximal aspect of the thrombus in dosages of 200,000 to 1,000,000 IU. In two patients with thrombus refractory to pharmacological thrombolytic treatment, mechanical wire microsnare maceration of the thrombus resulted in sinus patency. Radiological studies obtained 24 hours after thrombolysis reconfirmed sinus/vein patency in all patients. All patients' symptoms and neurological deficits improved, and no procedural complications ensued. Follow-up periods ranged from 12 to 35 months, and all six patients remain free of any symptomatic venous reocclusion. Factors including patients' age, preexisting medical conditions, and duration of symptoms had no statistical bearing on the outcome.

Conclusions. Patients with both dural and deep cerebral venous thrombosis often have a variable clinical course and an unpredictable neurological outcome. With recent improvements in interventional techniques, endovascular therapy is warranted in symptomatic patients early in the disease course, prior to morbid and potentially fatal neurological deterioration.

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Eric L. Zager, Ellen G. Shaver, Robert W. Hurst and Eugene S. Flamm

✓ Aneurysms of the distal anterior inferior cerebellar artery (AICA) are rare; fewer than 100 cases have been reported. The authors detail their experience with four cases and present endovascular as well as microsurgical management options.

The medical records and neuroimaging studies obtained in four patients who were treated at a single institution were reviewed. Clinical presentations, neuroimaging and intraoperative findings, and clinical outcomes were analyzed.

There were three men and one woman; their mean age was 43 years. Two patients presented with acute subarachnoid hemorrhage (SAH), and two presented with ataxia and vertigo (one with tinnitus, the other with hearing loss). Angiographic studies demonstrated aneurysms of the distal segment of the AICA. In one patient with von Hippel—Lindau syndrome and multiple cerebellar hemangioblastomas, a feeding artery aneurysm was found on a distal branch of the AICA. Three of the patients underwent successful surgical obliteration of their aneurysms, one by clipping, one by trapping, and one by resection along with the tumor. The fourth patient underwent coil embolization of the distal AICA and the aneurysm. All patients made an excellent neurological recovery.

Patients with aneurysms in this location may present with typical features of an acute SAH or with symptoms referable to the cerebellopontine angle. Evaluation with computerized tomography, magnetic resonance (MR) imaging, MR angiography, and digital subtraction angiography should be performed. For lesions distal to branches coursing to the brainstem, trapping and aneurysm resection are viable options that do not require bypass. Endovascular obliteration is also a reasonable option, although the possibility of retrograde thrombosis of the AICA is a concern.

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Uzma Samadani, Atsushi Umemura, Jurg L. Jaggi, Amy Colcher, Eric L. Zager and Gordon H. Baltuch

✓ Thalamic deep brain stimulation (DBS) has been demonstrated to be effective for the treatment of parkinsonian or essential tremor. To date, however, few data exist to support the application of this method to treat midbrain tremor.

A 24-year-old right-handed man underwent radiosurgery and subsequent resection of a recurrently hemorrhaging cavernous angioma located in the left side of the midbrain. The surgery exacerbated severe choreoathetotic resting and action tremors of his right extremities and trunk. The patient underwent placement of a deep brain stimulator into the left ventral intermediate nucleus of the thalamus (Vim). Postoperatively, decreased truncal ataxia and right-sided choreoathetotic tremor were demonstrated, with a 57% increase in dexterity as measured by task testing.

The authors demonstrate that DBS can be an effective treatment modality for disabling tremor after resection of a midbrain cavernous angioma.

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Mark G. Burnett and Eric L. Zager

Clinicians caring for patients with brachial plexus and other nerve injuries must possess a clear understanding of the peripheral nervous system's response to trauma. In this article, the authors briefly review peripheral nerve injury (PNI) types, discuss the common injury classification schemes, and describe the dynamic processes of degeneration and reinnervation that characterize the PNI response.

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H. Isaac Chen, Mark G. Burnett, Jason T. Huse, Robert A. Lustig, Linda J. Bagley and Eric L. Zager

✓Late cerebral radiation necrosis usually occurs within 3 years of stereotactic radiosurgery. The authors report on a case of recurrent radiation necrosis with rapid clinical deterioration and imaging findings resembling those of a malignant glioma. This 68-year-old man, who had a history of a left posterior temporal and thalamic arteriovenous malformation (AVM) treated with linear accelerator radiosurgery 13 years before presentation and complicated by radiation necrosis 11 years before presentation, exhibited new-onset mixed aphasia, right hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and an enlarging, heterogeneously enhancing mass in the region of the previously treated AVM. The patient was treated medically with corticosteroid agents, and stabilized temporarily. Unfortunately, his condition worsened precipitously soon thereafter, requiring the placement of a shunt for relief of obstructive hydrocephalus. Further surgical intervention was offered, but the patient’s family opted for hospice care instead. The patient died 10 weeks after initially presenting to the authors’ institution, and the results of an autopsy demonstrated radiation necrosis.

Symptomatic radiation necrosis can occur more than a decade after stereotactic radiosurgery, necessitating patient follow up during a longer period of time than currently practiced. Furthermore, there is a need for more careful reporting on the natural history of such cases to clarify the pathogenesis of very late and recurrent radiation necrosis after radiosurgery and to define patient groups with a higher risk for these entities.

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Jason H. Huang, Eric L. Zager, Jun Zhang, Robert F. Groff IV, Bryan J. Pfister, Akiva S. Cohen, M. Sean Grady, Eileen Maloney-Wilensky and Douglas H. Smith

Object

Although neuron transplantation to repair the nervous system has shown promise in animal models, there are few practical sources of viable neurons for clinical application and insufficient approaches to bridge extensive nerve damage in patients. Therefore, the authors sought a clinically relevant source of neurons that could be engineered into transplantable nervous tissue constructs. The authors chose to evaluate human dorsal root ganglion (DRG) neurons due to their robustness in culture.

Methods

Cervical DRGs were harvested from 16 live patients following elective ganglionectomies, and thoracic DRGs were harvested from 4 organ donor patients. Following harvest, the DRGs were digested in a dispase–collagenase treatment to dissociate neurons for culture. In addition, dissociated human DRG neurons were placed in a specially designed axon expansion chamber that induces continuous mechanical tension on axon fascicles spanning 2 populations of neurons originally plated ∼ 100 μm apart.

Results

The adult human DRG neurons, positively identified by neuronal markers, survived at least 3 months in culture while maintaining the ability to generate action potentials. Stretch-growth of axon fascicles in the expansion chamber occurred at the rate of 1 mm/day to a length of 1 cm, creating the first engineered living human nervous tissue constructs.

Conclusions

These data demonstrate the promise of adult human DRG neurons as an alternative transplant material due to their availability, viability, and capacity to be engineered. Also, these data show the feasibility of harvesting DRGs from living patients as a source of neurons for autologous transplant as well as from organ donors to serve as an allograft source of neurons.

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Shih-Shan Lang, Eric L. Zager, Thomas M. Coyne, Raj Nangunoori, J. Bruce Kneeland and Katherine L. Nathanson

In recent literature, there have been case reports of an extremely rare entity characterized by hybrid peripheral nerve tumors consisting of elements of neurofibroma, schwannoma, and/or perineurioma. The authors present a unique case of a patient with multiple painful hybrid tumors with negative genetic testing for neurofibromatosis Type 1 and no clinical evidence of neurofibromatosis Type 2 or schwannomatosis.

A 28-year-old woman presented with tentatively diagnosed schwannomatosis. She had painful bilateral retromastoid scalp tumors as well as multiple other painful tumors in the distribution of the saphenous, femoral, and sciatic nerves. Her family history was significant for a paternal grandfather with a solitary schwannoma. The patient underwent multiple surgical procedures for tumor resection, including tumors in the regions of the retromastoid scalp, bilateral sciatic nerves, left femoral nerve, and left axilla. These tumors were examined and evaluated histologically. Within the tumors, components of both neurofibromas and schwannomas were found, even though these 2 peripheral nerve sheath tumors have been long considered to be distinct entities. This case report suggests a distinct syndrome that has not previously been appreciated.