Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas.

OBJECTIVE: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin. METHODS: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset. RESULTS: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices. SIGNIFICANCE: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

High frequency oscillations are associated with cognitive processing in human recognition memory.

High frequency oscillations are associated with normal brain function, but also increasingly recognized as potential biomarkers of the epileptogenic brain. Their role in human cognition has been predominantly studied in classical gamma frequencies (30-100 Hz), which reflect neuronal network coordination involved in attention, learning and memory. Invasive brain recordings in animals and humans demonstrate that physiological oscillations extend beyond the gamma frequency range, but their function in human cognitive processing has not been fully elucidated. Here we investigate high frequency oscillations spanning the high gamma (50-125 Hz), ripple (125-250 Hz) and fast ripple (250-500 Hz) frequency bands using intracranial recordings from 12 patients (five males and seven females, age 21-63 years) during memory encoding and recall of a series of affectively charged images. Presentation of the images induced high frequency oscillations in all three studied bands within the primary visual, limbic and higher order cortical regions in a sequence consistent with the visual processing stream. These induced oscillations were detected on individual electrodes localized in the amygdala, hippocampus and specific neocortical areas, revealing discrete oscillations of characteristic frequency, duration and latency from image presentation. Memory encoding and recall significantly modulated the number of induced high gamma, ripple and fast ripple detections in the studied structures, which was greater in the primary sensory areas during the encoding (Wilcoxon rank sum test, P = 0.002) and in the higher-order cortical association areas during the recall (Wilcoxon rank sum test, P = 0.001) of memorized images. Furthermore, the induced high gamma, ripple and fast ripple responses discriminated the encoded and the affectively charged images. In summary, our results show that high frequency oscillations, spanning a wide range of frequencies, are associated with memory processing and generated along distributed cortical and limbic brain regions. These findings support an important role for fast network synchronization in human cognition and extend our understanding of normal physiological brain activity during memory processing.

Dysembryoplastic neuroepithelial tumor and calcifying pseudoneoplasms of the neuraxis: a collision of two seizure-associated lesions.

Dysembryoplastic neuroepithelial tumor (DNET) is a benign glioneuronal neoplasm typically associated with intractable, partial complex seizures in children and young adults. The authors present a case in which a DNET in a 45-year-old male was accompanied by a so-called "calcifying pseudoneoplasm of the neural axis" (CPNA), a rare tumefactive lesion considered reactive in nature. An MRI scan of the brain revealed a right temporal lobe abnormality with characteristics of DNT but no apparent calcification. Histologically, it exhibited classic features of DNET and an overlying meningeal- based, partially ossified, chondrocalcific lesion morphologically characteristic of CPNA. The association of DNET and CPNA has not been previously reported. The literature relevant to these two seizure-associated lesions is reviewed.

Adenovirus-mediated gene transfer to human cerebral arteries.

Gene therapy is being investigated as a putative treatment option for cardiovascular diseases, including cerebral vasospasm. Because there is presently no information regarding gene transfer to human cerebral arteries, the principal objective of this study was to characterize adenovirus-mediated expression and function of recombinant endothelial nitric oxide synthase (eNOS) gene in human pial arteries. Pial arteries (outer diameter 500 to 1,000 microm) were isolated from 30 patients undergoing temporal lobectomy for intractable seizures and were studied using histologic staining, histochemistry, electron microscopy, and isometric force recording. Gene transfer experiments were performed ex vivo using adenoviral vectors encoding genes for bovine eNOS (AdCMVeNOS) and Escherichia coli beta-galactosidase (AdCMVLacZ). In transduced arteries, studied 24 hours after exposure to vectors, expression of recombinant beta-galactosidase and eNOS was detected by histochemistry, localizing mainly to the adventitia (n = 4). Immunoelectron microscopy localized recombinant eNOS in adventitial fibroblasts. During contractions to U46619, bradykinin-induced relaxations were significantly augmented in AdCMVeNOS-transduced rings compared with control and AdCMVLacZ-transduced rings (P < 0.01; n = 6). The NOS inhibitor L-nitroarginine methylester (L-NAME) caused significantly greater contraction in AdCMVeNOS-transduced rings (P < 0.001; n = 4) and inhibited bradykinin-induced relaxations in control and transduced rings (P < 0.001; n = 6). The current findings suggest that in AdCMVeNOS-transduced human pial arteries, expression of recombinant eNOS occurs mainly in adventitial fibroblasts where it augments relaxations to NO-dependent agonists such as bradykinin. Findings from the current study might be beneficial in future clinical applications of gene therapy for the treatment or prevention of cerebral vasospasm.

Discontinuation of antiepileptic drugs after successful epilepsy surgery.

OBJECTIVE: To evaluate the frequency and risk factors for seizure recurrence subsequent to antiepileptic drug (AED) withdrawal in patients who underwent surgical treatment for intractable partial epilepsy and were rendered seizure-free. METHODS: The outcome of discontinuation of AED medication was studied retrospectively in 210 consecutive patients who were rendered seizure-free after epilepsy surgery performed between 1989 and 1993. RESULTS: Medical therapy was reduced in 96 patients and discontinued in 84 patients. The seizure recurrence rate after complete AED withdrawal was 14% and 36% at 2 and 5 years. In contrast, only 3% and 7% of the 30 patients who did not alter AED treatment after surgery had recurrent seizures in the same time intervals. After AED discontinuation, seizures tended to recur more often in patients with normal preoperative MRI studies compared with those with focal pathology. However, this difference did not reach significance. Intraoperative electrocorticography, extent of surgical resection, postoperative EEG, and seizure-free duration after surgery were not predictive of seizure outcome after AED withdrawal. CONCLUSIONS: AED withdrawal was associated with seizure recurrence in a significant portion of patients rendered seizure-free by epilepsy surgery. Patients with a normal preoperative MRI study showed a tendency for higher seizure recurrence, whereas the duration of seizure-free postoperative AED treatment interval did not significantly influence the seizure recurrence rate. These results will prove useful in counseling patients about discontinuing AED treatment after successful epilepsy surgery.

Surgery for focal epilepsy in the older patient.

Eight of the 237 patients who received a surgical procedure for intractable partial epilepsy at the Mayo Clinic during a 3-year period were 50 years of age or older. All patients had disabling partial seizures of several years in duration that were refractory to antiepileptic drug medication. A neuroimaging-identified epileptogenic lesion prompted referral for surgical treatment in three patients. The only clinically significant morbidity associated with surgery in the eight patients was a transient exacerbation of an aphasia in a patient who underwent a left frontal corticectomy. All eight patients had a favorable seizure outcome, and three patients postoperatively are seizure free. Epilepsy surgery may be an appropriate alternate therapy for select patients in the sixth decade of life or older with medically refractory partial seizures.

MRI assessments of hippocampal pathology in extratemporal lesional epilepsy.

We performed a prospective study in 18 patients to determine the extent of MRI-identified hippocampal pathology in patients with intractable partial epilepsy of extratemporal origin. A mesial temporal signal-intensity alteration or hippocampal formation (HF) atrophy, or both, have been shown to be reliable markers of the temporal lobe of seizure origin in patients with mesial temporal sclerosis. All patients subsequently received surgical ablative therapy between 1988 and 1992. During shortterm follow-up, 14 of the 18 patients experienced a significant reduction in seizure tendency, and 12 patients were rendered seizure-free. Qualitative and quantitative (HF volumetry) assessments of HF pathology were performed retrospectively by a blinded investigator. No hippocampal imaging alteration was present in 17 patients. Left HF atrophy was confirmed in one patient with post-traumatic epilepsy who underwent a successful right frontal lobectomy. Morphometric MRI studies rarely identify hippocampal pathology in patients with extratemporal epilepsy.

Traumatic occlusion of one limb of an intracranial arterial fenestration: an uncommon cause of stroke.

Three weeks after an automobile accident, a 35-year-old man experienced left throat and neck pain, numbness of the left face and tongue, dysphagia, left arm pain and weakness, and left miosis. At age 27, he had suffered an aneurysmal subarachnoid hemorrhage. Angiography at that time had also demonstrated a fenestration of the left intracranial vertebral artery. At the time of the second presentation, angiography showed that one of the limbs of the fenestration had become occluded. Although the vast majority of intracranial arterial fenestrations are asymptomatic, occlusion of one of the limbs of a fenestration may be the cause of stroke.

MRI hippocampal volumes and memory function before and after temporal lobectomy.

We investigated the relationship between preoperative MRI hippocampal volumes and clinical neuropsychological memory test data obtained before and after temporal lobectomy and amygdalohippocampectomy for intractable epilepsy in 44 left (LTL) and 36 right (RTL) temporal lobectomy patients. In LTL patients, the difference (right minus left hippocampal volume) between hippocampal volumes (DHF) was significantly (p < 0.001) correlated (r = 0.61) with postoperative verbal memory change as measured by a delayed memory percent retention score from the Wechsler Memory Scale-Revised, Logical Memory subtest. DHF was also positively associated with postoperative memory for abstract geometric designs in LTL patients (r = 0.49, p < 0.005). Resection of a relatively nonatrophic left hippocampus was associated with poorer verbal and visual memory outcome. In RTL patients, larger right adjusted (for total intracranial volume) hippocampal volume was associated with decline in visual-spatial learning, but not memory, following surgery. MRI hippocampal volume data appear to provide meaningful information in evaluating the risk for memory impairment following temporal lobectomy.

Therapeutic embolization angiography for extra-axial lesions in the head.

Percutaneous transcatheter arterial embolization has played an increasingly important role in the management of vascular lesions in the head. Embolization can promote thrombosis within vascular tumors and malformations, reduce bleeding and decrease the need for transfusion intraoperatively, and facilitate surgical approaches to otherwise unresectable lesions. It is important for the clinician to be aware of this interventional technique because many of the patients who are considered for embolization are triaged through several different clinical areas, and much can be gained from the collaboration of the clinician, the surgeon, and the angiographer. We performed 31 therapeutic particulate embolization procedures for extra-axial head lesions in 23 patients by using flow-directed techniques. Of these procedures, 11 resulted in vascular occlusion and 15 resulted in 80 to 95% obstruction, as demonstrated by angiography. In 14 patients, embolization was performed preoperatively both to decrease blood loss and to occlude inaccessible or unresectable portions of a lesion. In nine patients, embolization was the sole means of treatment for occluding an abnormal vascular shunt. Two patients (9%) experienced a minor transient neurologic change after the procedure.

Stereotactic resection of intra-axial cerebral lesions in partial epilepsy.

We performed a retrospective study of stereotactic resections of intra-axial brain mass lesions in 30 patients with intractable partial epilepsy. The most common pathologic alterations observed were vascular malformations (11 lesions) and glial neoplasms (11 lesions). The locations of the lesions included the postcentral gyrus in five patients, the precentral gyrus in five, and the deep-seated left posterior temporal region in four, all of which were sites that may have precluded standard craniotomy and cortical resection. Of the 30 medically refractory patients, 26 had at least an 80% reduction in seizure activity at a mean duration of follow-up of 22 months postoperatively. Nineteen of 22 patients with at least 1 year (mean, 28 months) of follow-up and 13 of 15 patients with at least 2 years (mean, 34 months) of follow-up had favorable surgical outcomes. "Lesionectomy" may allow pathologic examination of intracranial lesions and may produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.

Diagnosis and management of primary spinal epidural non-Hodgkin's lymphoma.

OBJECTIVE: To describe the diagnosis, management, and outcome in 10 patients with histologically confirmed primary spinal epidural non-Hodgkin's lymphoma. MATERIAL AND METHODS: We review the findings in a cohort of seven men and three women in whom this tumor was diagnosed between January 1979 and January 1993 and discuss the prognostic differences between primary and secondary spinal lymphomas. RESULTS: All patients (median age at diagnosis, 70 years) underwent a decompressive laminectomy, subtotal tumor resection, and spinal irradiation (median dose, 3,800 cGy). Nine of 10 tumors were of B-cell origin. Six patients are alive and well. In four patients, recurrent disease developed from 15 to 62 months after the original diagnosis; of these, one has died. The median duration of survival of all patients was 42 months; of those living more than 24 months after diagnosis, the median duration of survival was 80 months. CONCLUSION: A rapidly progressive spinal cord or cauda equina syndrome with neuroimaging findings consistent with an extradural compressive lesion should alert caregivers to the possibility of spinal epidural lymphoma. Although the prognosis for patients with secondary spinal epidural non-Hodgkin's lymphoma is often poor, primary spinal epidural non-Hodgkin's lymphoma can be associated with a favorable outcome if diagnosed and treated early.

Carotid endarterectomy in patients with contralateral carotid occlusion.

In this study, we assessed the results of carotid endarterectomy in 357 patients with a carotid stenosis and contralateral carotid occlusion. The overall major neurologic morbidity was 0.6%, and the minor morbidity was 1.1%. The causes of four perioperative deaths (1.1%) were myocardial infarction in two patients, ruptured abdominal aortic aneurysm in one, and respiratory complications in one. Therefore, an excellent result was achieved in 97.2% of patients. With occlusion of the carotid artery for the endarterectomy, 165 patients (46%) had appreciable attenuation in intraoperative electroencephalographic findings and a decrease in cerebral blood flow to approximately 10 ml/100 g of brain tissue per min that necessitated placement of a shunt. This high percentage of profound electroencephalographic and blood flow changes during carotid occlusion suggests that the potential for collateral blood flow in this group of patients is minimal. These results demonstrate that a carotid endarterectomy can be performed at low risk in patients with a contralateral carotid occlusion. We advocate annual noninvasive carotid testing for patients with asymptomatic carotid stenosis and contralateral carotid occlusion. If progression of the stenosis is evident, a prophylactic endarterectomy should be considered because these patients may have a higher risk for cerebral infarction than do patients with a unilateral asymptomatic stenosis.

Clinical and radiographic features of dural arteriovenous fistula, a treatable cause of myelopathy.

OBJECTIVE: To assess presentation, imaging, treatment, and outcome of patients with myelopathy due to a dural arteriovenous fistula (DAVF). PATIENTS AND METHODS: This retrospective review identified 94 patients with DAVF surgically treated at our institution between June 1985 and December 1999. The mean ages of the 75 men and 19 women were 62.6 years and 63.0 years, respectively (range, 31-83 years). Magnetic resonance imaging was performed in 87 patients, computed tomography-myelography was performed in 37 patients, and spinal angiography was performed in all patients. Initial examination findings were retrospectively adjusted to a modified Aminoff-Logue myelopathy scale. RESULTS: Of the 94 patients, 47 presented with symptoms that worsened with erect posture or Valsalva maneuver. As myelopathy progressed, patients' symptoms increased, and 6 patients had paraplegia at presentation. The mean time from symptom onset to diagnosis was 23 months (range, 2-120 months). Magnetic resonance imaging confirmed the diagnosis in 86 patients; computed tomography-myelography was needed to confirm the fistula in 1 patient. Spinal angiography detected the fistula in all patients. Surgical obliteration of the DAVF was successful in 93 patients; in 1 patient surgery failed because the DAVF was not localized, but acrylic endovascular embolization was successful. No patient experienced permanent morbidity or mortality. Of the 94 patients, 93 improved postoperatively 1 or 2 levels based on a modified Aminoff-Logue scale. Older patients with severe long-term deficits had poor outcomes. CONCLUSIONS: The diagnosis of a DAVF seems to be delayed considerably because DAVF is not included in the differential diagnosis of myelopathy and because of clinicians' unfamiliarity with suggestive or revealing findings on diagnostic imaging. Neurodiagnostic imaging confirms the diagnosis, and spinal angiography localizes the fistula. Surgical intradural disconnection of the DAVF clinically reverses the pathophysiology. Additionally, surgical treatment is associated with low short-term morbidity, no permanent morbidity, and no mortality. If the diagnosis is made early and treatment initiated in such patients, they generally do well.

Selective posterior cerebral artery injection of amytal: new method of preoperative memory testing.

The carotid Amytal test (Wada test) was introduced, in 1948 by Wada, to localize speech function before temporal lobectomy in patients with medically refractory epilepsy, and it remains the standard for that purpose. The same test has also been used since 1962 to evaluate memory function; however, the adequacy of the test in this application has been viewed with increasing skepticism in recent years. Therefore, we developed an alternative to the Wada test. It consists of selective injection of Amytal into the posterior cerebral artery (PCA). This PCA Amytal test is designed to test only memory function (not language). We present several anatomic and functional reasons why this approach should be superior to the Wada test for this purpose. We also present preliminary data in support of this hypothesis. To date, we have had successful results of the PCA Amytal test in 38 of 45 patients (84%), and one major complication has occurred (2%).

Treatment of tumors involving the anterior cranial fossa.

The potential for a tumor of the upper face, either malignant or nonmalignant, to involve the anterior cranial base is often not appreciated. This leads to inadequate preoperative investigation and to surgery performed by the head and neck surgeon without the help of the neurosurgeon. In this way, complete tumor resection may be compromised or delayed. Neither of these situations is desirable. If the potential for anterior cranial fossa invasion is recognized, there should be prior consultation with the neurosurgeon and a combined operative procedure. Exposure of these lesions has considerably improved with experience in congenital craniofacial deformities: this will allow en bloc resection of most pathologies. Immediate reconstruction after resection of nonmalignant tumors is advocated, but in aggressive--particularly in recurrent--malignancies, delayed reconstruction is advised. Careful combined follow-up with frequent blind biopsies should be carried out as indicated.

Spinal dural arteriovenous fistulas: MR and myelographic findings.

PURPOSE: To examine the clinical and radiographic findings in a large group of patients having or suspected of having a spinal dural arteriovenous fistula. METHODS: An analysis of 240 spinal angiograms in 132 patients revealed 97 vascular malformations that included 66 spinal dural arteriovenous fistulas. Sixteen patients had 1 or more normal spinal angiograms that were performed for suspected spinal dural arteriovenous fistulas on other imaging studies. The imaging and clinical data were reviewed in all patients who had or were suspected of having a spinal dural arteriovenous fistula and who had a spinal MR (n = 44) and a myelogram (n = 37). RESULTS: Spinal dural arteriovenous fistulas were more common in males (3.4:1) with an average age of 62 years (range, 37 to 81 years). The average time from onset of symptoms to diagnosis was 27 months. Clinical findings included weakness (55%), a progressive clinical course (100%), and a myelopathy on exam (84%). The nidus of the fistula was located between T-6 and T-12 in 61%, in the sacrum in 9%, and intracranially in 8%. In the spinal dural arteriovenous fistula group, vessels were seen on supine myelography in all patients. MR findings in this group included increased T2 signal in the cord (100%), gadolinium enhancement (88%), mass effect (45%), and flow voids (T1, 35%; T2, 45%). The patients in the negative spinal angiogram group were younger (average age, 51 years), had symptoms longer (average time from symptom onset to spinal angiogram, 59 months), and presented with numbness or pain (76%). When compared with the patients with spinal dural arteriovenous fistula, acute or stable deficits were more common (31%), and myelopathy on exam was less common (56%). Although the angiogram-negative patients commonly had vessels on the myelogram (92%), abnormal T2 signal in the cord was unusual (17%). CONCLUSIONS: In the appropriate clinical setting, high T2 signal of the spinal cord is the most sensitive imaging finding in spinal dural arteriovenous fistula. The presence of mass effect and enhancement should not discourage this diagnosis. The likelihood of finding a spinal dural arteriovenous fistula in a patient without T2 signal on MR is low.

Assessment of functional MR imaging in neurosurgical planning.

BACKGROUND AND PURPOSE: Presurgical sensorimotor mapping with functional MR imaging is gaining acceptance in clinical practice; however, to our knowledge, its therapeutic efficacy has not been assessed in a sizable group of patients. Our goal was to identify how preoperative sensorimotor functional studies were used to guide the treatment of neuro-oncologic and epilepsy surgery patients. METHODS: We retrospectively reviewed the medical records of 46 patients who had undergone preoperative sensorimotor functional MR imaging to document how often and in what ways the imaging studies had influenced their management. Clinical management decisions were grouped into three categories: for assessing the feasibility of surgical resection, for surgical planning, and for selecting patients for invasive functional mapping procedures. RESULTS: Functional MR imaging studies successfully identified the functional central sulcus ipsilateral to the abnormality in 32 of the 46 patients, and these 32 patients are the focus of this report. In epilepsy surgery candidates, the functional MR imaging results were used to determine in part the feasibility of a proposed surgical resection in 70% of patients, to aid in surgical planning in 43%, and to select patients for invasive surgical functional mapping in 52%. In tumor patients, the functional MR imaging results were used to determine in part the feasibility of surgical resection in 55%, to aid in surgical planning in 22%, and to select patients for invasive surgical functional mapping in 78%. Overall, functional MR imaging studies were used in one or more of the three clinical decision-making categories in 89% of tumor patients and 91% of epilepsy surgery patients. CONCLUSION: Preoperative functional MR imaging is useful to clinicians at three key stages in the preoperative clinical management paradigm of a substantial percentage of patients who are being considered for resective tumor or epilepsy surgery.

Prolonged bleeding time associated with moxalactam administration.

A case of moxalactam-induced coagulopathy is reported. The authors think that this coagulopathy is caused by an effect on platelet aggregation and not by inhibition of vitamin K-dependent clotting factors. It is recommended that bleeding times be routinely checked preoperatively in patients being treated with moxalactam.

Magnetic resonance imaging in syringomyelia.

Myelography and myelography assisted with computed tomography have been the most commonly used radiographic methods in the study of syringomyelia. These studies have never been entirely reliable in demonstrating the syrinx cavity and its relationship to other intracranial structures. During the 1st year of operation of the magnetic resonance imaging facility, the syringomyelic cavity was demonstrated in 15 patients who all had typical clinical signs and symptoms associated with syringomyelia. Nine cases were syringomyelia with Chiari malformation. One case showed additional hydrocephalus. Four cases were idiopathic, and 1 case was remotely posttraumatic. Magnetic resonance imaging, although it is in its infancy, already promises to be the most important radiographic technique for syringomyelia because it provides an anatomically truthful visualization of the sagittal plane of the cervical cord and can demonstrate the syrinx cavity and its relationship with the cerebellar tonsils, the 4th ventricle, and other related structures.