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Bassam Hadi, Y. Ping Zhang, Darlene A. Burke, Christopher B. Shields, and David S. K. Magnuson

Object. The aims of this study were to investigate further the role played by lumbar spinal cord interneurons in the generation of locomotor activity and to develop a model of spinal cord injury suitable for testing neuron replacement strategies.

Methods. Adult rats received intraspinal injections of kainic acid (KA). Locomotion was assessed weekly for 4 weeks by using the Basso, Beattie, and Bresnahan (BBB) 21-point locomotor scale, and transcranial magnetic motor evoked potentials (MMEPs) were recorded in gastrocnemius and quadriceps muscles at 1 and 4 weeks. No changes in transcranial MMEP latency were noted following KA injection, indicating that the descending motor pathways responsible for these responses, including the alpha motor neurons, were not compromised. Rats in which KA injections included much of the L-2 segment (10 animals) showed severe locomotor deficits, with a mean BBB score of 4.5 ± 3.6 (± standard deviation). Rats that received lesions rostral to the L-2 segment (four animals) were able to locomote and had a mean BBB score of 14.6 ± 2.6. Three rats that received only one injection bilaterally centered at L-2 (three animals) had a mean BBB score of 3.2 ± 2. Histological examination revealed variable loss of motor neurons limited to the injection site. There was no correlation between motor neuron loss and BBB score.

Conclusions. Interneuron loss centered on the L-2 segment induces lasting paraplegia independent of motor neuron loss and white matter damage, supporting earlier suggestions that circuitry critical to the generator of locomotor activity (the central pattern generator) resides in this area. This injury model may prove ideal for studies of neuron replacement strategies.

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Kai Zhang, Sanjay Bhatia, Michael Y. Oh, David Cohen, Cindy Angle, and Donald Whiting

Object

Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) has proven to be efficacious in the treatment of essential tremor (ET). The authors report on long-term follow-up of a series of patients treated at 1 institution by 1 neurosurgeon.

Methods

Thirty-four patients with ET received unilateral or bilateral VIM DBS. The tremor and handwriting components of the Fahn-Tolosa-Marin clinical tremor rating scale were assessed pre- and postoperatively. Visual analog scale scores for overall patient satisfaction and tremor control were recorded. Stimulation parameters at different intervals after surgery were also recorded.

Results

The average follow-up period was 56.9 months. The average tremor score improved from 3.27 preoperatively to 0.64 postoperatively (on stimulation; p < 0.001) and the average handwriting score improved from 2.94 to 0.89 (p < 0.001). The average visual analog scale score for overall satisfaction was 8.12 and for tremor control was 1.43. Overall, there was an 80.4% improvement in tremor and 69.7% improvement in handwriting. In 12 patients both tremor and handwriting scores were compared between 57.3 months and 90.7 months after surgery and no significant changes were discovered. Comparison of stimulation parameters at onset and at 1–3, 3–5, 5–7, and > 7 years after surgery showed significant differences, with a gradual increase in stimulation parameters within 5 years after surgery. The overall hardware-related complication rate was 23.5%.

Conclusions

Deep brain stimulation of the VIM is an efficient and safe treatment for ET. Tremor and handwriting improvements in long-term follow-up are stable. The patients' perception of their outcome is quite good. However, tolerance may develop in some patients requiring changes in stimulation parameters.

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Kotaro Ogihara, Alexander Y. Zubkov, David H. Bernanke, Adam I. Lewis, Andrew D. Parent, and John H. Zhang

Object. Oxyhemoglobin (OxyHb) is one of the most important spasmogens for cerebral vasospasm that follows aneurysmal subarachnoid hemorrhage. The cytotoxic effect of OxyHb has been documented in endothelial and smooth-muscle cells; however, the pattern of cell death—necrosis or apoptosis—as the final stage of cell damage has not been demonstrated. This study was undertaken to determine if OxyHb induces apoptotic changes in cultured bovine aortic endothelial cells.

Methods. Confluent bovine aortic endothelial cells were treated with OxyHb in a concentration- and time-dependent manner. Cell density was assayed by counting the number of cells that attached to culture dishes after exposure to OxyHb. To identify apoptotic changes, the investigators used three specific methods: DNA fragmentation (electrophoreses), the apoptotic body (transmission electron microscopy), and cleavage of poly (adenosine diphosphate ribose) polymerase (PARP [Western blotting]).

Conclusions. Oxyhemoglobin decreased cell density in a concentration- and time-dependent manner. Analysis of DNA showed a pattern of internucleosomal cleavage characteristic of apoptosis (DNA ladder). Transmission electron microscopy demonstrated condensation of nuclei and apoptotic bodies in OxyHb-treated endothelial cells. Western blotting with the PARP antibody revealed that the 116-kD PARP was cleaved to the 85-kD apoptosis-related fragment. These results for the first time demonstrated that the OxyHb induces apoptosis in cultured endothelial cells.

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Shih-Shan Lang, Nankee K. Kumar, Chao Zhao, David Y. Zhang, Alexander M. Tucker, Phillip B. Storm, Gregory G. Heuer, Avi A. Gajjar, Chong Tae Kim, Ian Yuan, Susan Sotardi, Todd J. Kilbaugh, and Jimmy W. Huh

OBJECTIVE

Severe traumatic brain injury (TBI) is a leading cause of disability and death in the pediatric population. While intracranial pressure (ICP) monitoring is the gold standard in acute neurocritical care following pediatric severe TBI, brain tissue oxygen tension (PbtO2) monitoring may also help limit secondary brain injury and improve outcomes. The authors hypothesized that pediatric patients with severe TBI and ICP + PbtO2 monitoring and treatment would have better outcomes than those who underwent ICP-only monitoring and treatment.

METHODS

Patients ≤ 18 years of age with severe TBI who received ICP ± PbtO2 monitoring at a quaternary children’s hospital between 1998 and 2021 were retrospectively reviewed. The relationships between conventional measurements of TBI were evaluated, i.e., ICP, cerebral perfusion pressure (CPP), and PbtO2. Differences were analyzed between patients with ICP + PbtO2 versus ICP-only monitoring on hospital and pediatric intensive care unit (PICU) length of stay (LOS), length of intubation, Pediatric Intensity Level of Therapy scale score, and functional outcome using the Glasgow Outcome Score–Extended (GOS-E) scale at 6 months postinjury.

RESULTS

Forty-nine patients, including 19 with ICP + PbtO2 and 30 with ICP only, were analyzed. There was a weak negative association between ICP and PbtO2 (β = −0.04). Conversely, there was a strong positive correlation between CPP ≥ 40 mm Hg and PbtO2 ≥ 15 and ≥ 20 mm Hg (β = 0.30 and β = 0.29, p < 0.001, respectively). An increased number of events of cerebral PbtO2 < 15 mm Hg or < 20 mm Hg were associated with longer hospital (p = 0.01 and p = 0.022, respectively) and PICU (p = 0.015 and p = 0.007, respectively) LOS, increased duration of mechanical ventilation (p = 0.015 when PbtO2 < 15 mm Hg), and an unfavorable 6-month GOS-E score (p = 0.045 and p = 0.022, respectively). An increased number of intracranial hypertension episodes (ICP ≥ 20 mm Hg) were associated with longer hospital (p = 0.007) and PICU (p < 0.001) LOS and longer duration of mechanical ventilation (p < 0.001). Lower minimum hourly and average daily ICP values predicted favorable GOS-E scores (p < 0.001 for both). Patients with ICP + PbtO2 monitoring experienced longer PICU LOS (p = 0.018) compared to patients with ICP-only monitoring, with no significant GOS-E score difference between groups (p = 0.733).

CONCLUSIONS

An increased number of cerebral hypoxic episodes and an increased number of intracranial hypertension episodes resulted in longer hospital LOS and longer duration of mechanical ventilator support. An increased number of cerebral hypoxic episodes also correlated with less favorable functional outcomes. In contrast, lower minimum hourly and average daily ICP values, but not the number of intracranial hypertension episodes, were associated with more favorable functional outcomes. There was a weak correlation between ICP and PbtO2, supporting the importance of multimodal invasive neuromonitoring in pediatric severe TBI.