Anthony M. Kaufmann

Ischemic Core and Penumbra in Human Stroke

Background and Purpose—The ischemic core and penumbra have not been thoroughly characterized after acute cerebral thromboembolic occlusion in humans. Differentiation between areas of potentially viable and irreversibly injured ischemic tissue may facilitate assessment and treatment of stroke patients. Methods—Cerebral blood flow (CBF) was measured in 20 patients with acute middle cerebral artery (MCA) occlusion between 60 and 360 minutes after stroke onset, with the stable xenon computerized tomography (CT) technique. Threshold displays were generated at a single level, and the percentages of hemisphere with CBF ≤6, ≤10, 11 to 20, 21 to 30, and >30 cm3 · 100 g−1 · min−1 were measured. The corresponding images on 12 available follow-up CT scans were similarly assessed to determine the area of final infarct. Comparisons were analyzed with a paired Student’s t test and Pearson’s correlation coefficient. Results—Discrete and confluent areas of CBF ≤20 cm3 · 100 g−1 · min−1 were identified in all patients, ips...

Traumatic basilar aneurysm after endoscopic third ventriculostomy: case report.

OBJECTIVE AND IMPORTANCE: This case illustrates that although endoscopic third ventriculostomy for patients with aqueductal stenosis is successful and minimally invasive, it can have severe, life-threatening complications. CLINICAL PRESENTATION: A 3-year-old girl presented with hydrocephalus and aqueductal stenosis. She underwent endoscopic third ventriculostomy with laser fenestration of the third ventricular floor. During the procedure, she developed a severe intraventricular hemorrhage that required prolonged external ventricular drainage and ultimately ventriculoperitoneal shunting. Despite having a negative angiogram after the procedure, she presented 1 month later with a subarachnoid hemorrhage and a traumatic basilar tip aneurysm. INTERVENTION: The patient underwent a right subtemporal approach with clip ligation of the aneurysm and subsequently had a good recovery. CONCLUSION: Hemorrhagic complications after endoscopic third ventriculostomy are rare. The formation of a traumatic basilar tip aneurysm after this procedure has not been reported in the literature. Laser fenestration of the third ventricular floor may increase the risk of this event.

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study.

The relationship of blood velocity as measured by transcranial doppler ultrasonography to cerebral blood flow as determined by stable xenon computed tomographic studies after aneurysmal subarachnoid hemorrhage.

Transcranial doppler (TCD) ultrasonography is often used to guide the management of patients with subarachnoid hemorrhage (SAH). However, the correlation between increased blood velocity as measured by TCD ultrasonography and angiographic vasospasm was established before the routine use of hypervolemia/hemodilution and administration of nimodipine and did not address blood flow. The relationship of blood velocity as measured by TCD ultrasonography and local cerebral blood flow (LCBF) in SAH managed with these modalities is unknown. Patients presenting with aneurysmal SAH between January 1992 and September 1993 who underwent TCD ultrasonography and xenon computed tomographic (Xe/CT) LCBF studies within 12 hours were retrospectively studied. Fifty patients underwent a total of 94 paired studies, encompassing 709 vascular territories. All were treated with nimodipine and hypervolemia/hemodilution. Hematocrit, blood pressure, and partial carbon dioxide pressure were similar at the time of TCD ultrasonography and Xe/CT measurement of LCBF. When LCBF in the middle cerebral artery (MCA) was < or = 31 ml/100 g/min, the corresponding peak systolic velocity measured by TCD ultrasonography was 119 cm/s, whereas those > 31 ml/100 g/min had a velocity of 169 cm/s (P = 0.006). High LCBF was associated with high velocity in all vascular territories, reaching significance in all but the internal carotid artery. At the time of each study, 41 neurological examinations were focal and 53 were nonfocal. The Xe/CT measurement of LCBF in the MCA contralateral to a deficit was significantly less than in territories without corresponding clinical deficits (P = 0.01), whereas peak systolic velocities in the MCA were not significantly different (P = 0.71). Territories with increases in blood velocity in the MCA of > 50 cm/s/24 h did not have statistically different LCBF (P = 0.183). Our results suggest that increased blood velocity revealed by TCD ultrasonography correlates with increased LCBF and not with ischemia. No difference in LCBF was found in territories with and without rapid increases in blood velocity in the MCA. Furthermore, although focal neurological deficits corresponded with decreased contralateral LCBF in the MCA, increased velocity did not correlate with neurological findings. Therapeutic decisions based solely on blood velocity revealed by TCD ultrasonography might be inappropriate and potentially harmful. Xe/CT studies of LCBF are useful in guiding the management of SAH.

Neurovascular compression findings in hemifacial spasm

OBJECT It is generally accepted that hemifacial spasm (HFS) is caused by pulsatile vascular compression upon the facial nerve root exit zone. This 2-3 mm area, considered synonymous with the Obersteiner-Redlich zone, is a transition zone (TZ) between central and peripheral axonal myelination that is situated at the nerves detachment from the pons. Further proximally, however, the facial nerve is exposed on the pontine surface and emerges from the pontomedullary sulcus. The incidence and significance of neurovascular compression upon these different segments of the facial nerve in patients with HFS has not been previously reported. METHODS The nature of neurovascular compression was determined in 115 consecutive patients undergoing their first microvascular decompression (MVD) for HFS. The location of neurovascular compression was categorized to 1 of 4 anatomical portions of the facial nerve: RExP = root exit point; AS = attached segment; RDP = root detachment point that corresponds to the TZ; and CP = distal cisternal portion. The severity of compression was defined as follows: mild = contact without indentation of nerve; moderate = indentation; and severe = deviation of the nerve course. Success in alleviating HFS was documented by telephone interview conducted at least 24 months following MVD surgery. RESULTS Neurovascular compression was found in all patients, and the main culprit was the anterior inferior cerebellar artery (in 43%), posterior inferior cerebellar artery (in 31%), vertebral artery (in 23%), or a large vein (in 3%). Multiple compressing vessels were found in 38% of cases. The primary culprit location was at RExP in 10%, AS in 64%, RDP in 22%, and CP in 3%. The severity of compression was mild in 27%, moderate in 61%, and severe in 12%. Failure to alleviate HFS occurred in 9 cases, and was not related to compression location, severity, or vessel type. CONCLUSIONS The authors observed that culprit neurovascular compression was present in all cases of HFS, but situated at the RDP or Obersteiner-Redlich zone in only one-quarter of cases and rarely on the more distal facial nerve root. Since the majority of culprit compression was found more proximally on the pontine surface or even pontomedullary sulcus origin of the facial nerve, these areas must be effectively visualized to achieve consistent success in performing MVD for HFS.

Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

BACKGROUND Intra-arterial papaverine (IAP) has been described as a treatment for cerebral vasospasm refractory to standard therapy. METHODS We report a series of 15 consecutive patients with aneurysmal subarachnoid hemorrhage in which IAP was employed for the treatment of symptomatic vasospasm. All patients exhibited delayed ischemic neurologic deficits, focal cerebral hypoperfusion on stable xenon-enhanced computerized tomography cerebral blood flow studies, and angiographically defined arterial narrowing. Papaverine was infused into 32 arteries on 23 occasions. Six patients required multiple treatments between 1 and 8 days apart. In five instances, IAP was combined with angioplasty. RESULTS Angiographically defined vasospasm was at least partially reversed immediately following treatment on 18 of 23 occasions. The associated clinical improvement was major on 6 occasions, and either minor or none on 17. Post-treatment cerebral blood flow was assessed on 13 occasions and showed improvement in previously ischemic areas on six occasions and no improvement on seven. Complications were encountered on four occasions. Systemic hypotension and transient brain-stem depression were seen with vertebral artery infusions; a generalized seizure and paradoxical aggravation of vasospasm resulting in hemispheric infarction occurred with internal carotid artery infusions. CONCLUSIONS Intra-arterial papaverine resulted in reversal of arterial narrowing in the majority of cases (78%). However, this angiographic improvement was associated with cerebral blood flow augmentation in only 46% of cases analyzed, and major clinical improvement in 26%.

Quantitative Cerebral Blood Flow Determinations in Acute Ischemic Stroke Relationship to Computed Tomography and Angiography

BACKGROUND AND PURPOSE The advent of new modalities to treat acute ischemic stroke presents the need for accurate, early diagnosis. In acute ischemic stroke, CT scans are frequently normal or reveal only subtle hypodense changes. This study explored the utility and increased sensitivity of xenonenhanced CT (XeCT) in the diagnosis of acute cerebral ischemia and investigated the relationship between cerebral blood flow (CBF) measurements and early CT and angiographic findings in acute stroke. METHODS The CT scans, XeCT scans, and angiograms of 20 patients who presented within 6 hours of acute anterior circulation ischemic strokes were analyzed. RESULTS CT scans were abnormal in 11 (55%) of 20 patients. XeCT scans were abnormal in all 20 (100%) patients, showing regions of interest with CBF < 20 (mL/100 g per minute) in the symptomatic middle cerebral artery (MCA) territories. The mean CBF in the symptomatic MCA territories was significantly lower than than of the asymptomatic MCA territories (P < .0005). In patients with basal ganglia hypodensities, the mean symptomatic MCA territory CBF was significantly lower than that of patients who did not exhibit these early CT findings (P < .05). The mean symptomatic MCA territory CBF in patients with angiographic M1 occlusions was significantly lower than that of patients whose infarcts were caused by MCA branch occlusions (P < .01). CONCLUSIONS These results show that XeCT is more sensitive than CT in detecting acute strokes and that CBF measurements correlate with early CT and angiographic findings. XeCT may allow for the hyperacute identification of subsets of patients with acute ischemic events who are less likely to benefit and more likely to derive complications from aggressive stroke therapy.

Stereotactic radiosurgery for intractable cluster headache: an initial report from the North American Gamma Knife Consortium

OBJECT The aim of this study was to evaluate the outcomes of Gamma Knife surgery (GKS) when used for patients with intractable cluster headache (CH). METHODS Four participating centers of the North American Gamma Knife Consortium identified 17 patients who underwent GKS for intractable CH between 1996 and 2008. The median patient age was 47 years (range 26-83 years). The median duration of pain before GKS was 10 years (range 1.3-40 years). Seven patients underwent unsuccessful prior surgical procedures, including microvascular decompression (2 patients), microvascular decompression with glycerol rhizotomy (2 patients), deep brain stimulation (1 patient), trigeminal ganglion stimulation (1 patient), and prior GKS (1 patient). Fourteen patients had associated autonomic symptoms. The radiosurgical target was the trigeminal nerve (TN) root and the sphenopalatine ganglion (SPG) in 8 patients, only the TN in 8 patients, and only the SPG in 1 patient. The median maximum TN and SPG dose was 80 Gy. RESULTS Favorable pain relief (Barrow Neurological Institute Grades I-IIIb) was achieved and maintained in 10 (59%) of 17 patients at a median follow-up of 34 months. Three patients required additional procedures (repeat GKS in 2 patients, hypothalamic deep brain stimulation in 1 patient). Eight (50%) of 16 patients who had their TN irradiated developed facial sensory dysfunction after GKS. CONCLUSIONS Gamma Knife surgery for intractable, medically refractory CH provided lasting pain reduction in approximately 60% of patients, but was associated with a significantly greater chance of facial sensory disturbances than GKS used for trigeminal neuralgia.

Periodontoid Synovial Cyst Causing Cervico-medullary Compression

BACKGROUND Periodontoid synovial cysts are rare lesions which may produce symptomatic cervico-medullary compression. METHOD We report such a patient, whose progressive neurological deterioration required surgical treatment by transoral odontoidectomy and decompression. RESULTS The diagnostic and theraputic interventions are described, including a lumbar puncture which precipitated a transient loss of consciousness and respiratory arrest. Surgery achieved clinical improvement, without complications or need for operative stablization. Detailed neuropathology is presented, as well as a literature review. CONCLUSION Appropriate neuroradiological assessment is required in patients with suspected cervico-medullary compression, and symptomatic periodontoid synovial cysts may respond well to transoral surgical decompression.

Recombinant factor VIIa plus surgery for intracerebral hemorrhage.

BACKGROUND Hyperacute surgical evacuation of intracerebral hemorrhage is associated with a high rebleeding rate. The peri-operative administration of rFVIIa to patients with intracerebral hemorrhage may decrease the frequency of post-operative hemorrhage, and improve outcome. METHODS Patients receiving recombinant activated factor VII (rFVIIA) therapy immediately prior to acute surgery were collected at two centres. The intracerebral hemorrhage (ICH) score and ICH Grading Scale were determined, as was long-term outcome using the modified Rankin Scale. Residual/recurrent clot was evaluated by comparing pre-operative to post-operative CT scans. RESULTS Fifteen patients with intracerebral hemorrhage received 40-90 microg/kg of rFVIIa and underwent surgical hematoma evacuation at a median time of five hours following symptom onset. Median pre-operative clot volume was 60 ml, decreasing to 2 ml post-operatively. There were no thromboembolic adverse events. Thirteen patients survived, 11 (73%) were independent, and two (13%) had a moderate to severe disability. These outcomes were significantly better than expected based on the median ICH score (40% mortality) and based on median ICH Grading Scale (18% good outcome). CONCLUSIONS The pre or perioperative administration of rFVIIa resulted in minimal residual or recurrent hematoma volume and may be an important adjunct to surgery in patients with intracerebral hemorrhage.