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Scott Y. Rahimi, John H. Brown, Samuel D. Macomson, Michael A. Jensen and Cargill H. Alleyne Jr.

✓ Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is a disease process for which the lack of effective treatments has plagued neurosurgeons for decades. Historically, successful treatment after SAH in the acute setting was often followed by a rapid, uncontrollable deterioration in the subacute interval. Little was known regarding the nature and progression of this condition until the mid-1800s, when the disease was first described by Gull. Insight into the origin and natural history of cerebral vasospasm came slowly over the next 100 years, until the 1950s. Over the past five decades our understanding of cerebral vasospasm has expanded exponentially. This newly discovered information has been used by neurosurgeons worldwide for successful treatment of complications associated with vasospasm. Nevertheless, although great strides have been made toward elucidating the causes of cerebral vasospasm, a lasting cure continues to elude experts and the disease continues to wreak havoc on patients after aneurysmal SAH.

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Elizabeth J. Furnish, Colleen M. Brophy, Valerie A. Harris, Samuel Macomson, Julia Winger, Geoffrey A. Head and Ellen G. Shaver

Object

Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent linkage to cell permeant peptides (CPPs). The hypothesis of this study was that either intrathecal or intravenous delivery of a phosphopeptide mimetic of the small heat shock–related protein, HSP20, linked to a CPP, would inhibit delayed decreases in cerebral perfusion after experimental SAH in a rat model.

Methods

This study was conducted in 3 parts: 1) prevention and 2) reversal of delayed decreases in cerebral perfusion via either intrathecal or intravenous administration of a CPP linked to phosphopeptide mimetics of HSP20 (AZX100) and 3) determining the effect of intravenous administration of AZX100 on blood pressure and heart rate. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Subsequently, AZX100 was administered intrathecally via a cisternal catheter or intravenously. Cerebral perfusion was determined by laser Doppler monitoring. Blood pressure was monitored by telemetry in a separate group of naïve animals treated with AZX100 for 24 hours.

Results

The maximal decrease in cerebral perfusion occurred 3 days after SAH. Cisternal administration of AZX100 (0.14–0.57 mg/kg) 24 hours after hemorrhage prevented decreases in cerebral perfusion after SAH. Animals receiving lower doses of AZX100 (0.068 mg/kg) or a scrambled sequence of the active HSP20 peptide linked to CPP developed decreases in cerebral perfusion similar to those seen in control animals. Intravenous administration of AZX100 (1.22 mg/kg) 24 hours after hemorrhage prevented the decreases in cerebral perfusion seen in the controls. Intravenous administration (0.175 mg/kg and 1.22 mg/kg) of AZX100 on Days 2 and 3 after SAH reversed decreases in cerebral perfusion as early as Day 3. There was no impact of AZX100 on blood pressure or heart rate at doses up to 2.73 mg/kg.

Conclusions

Cisternal administration of AZX100 24 hours after hemorrhage prevented decreases in cerebral perfusion. Intravenous administration of AZX100 also prevented and reversed decreases in cerebral perfusion at doses that did not induce hypotension. Transduction of biologically active motifs of downstream regulators like HSP20 represents a potential novel treatment for SAH.

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Sydney M. Hester, John F. Fisher, Mark R. Lee, Samuel Macomson and John R. Vender

Object

Intrathecal baclofen therapy has been used successfully for intractable spasticity in children with cerebral palsy. Infections are rare, but they are potentially life threatening if complicated by bacteremia or meningitis. Treatment without removal of the system is desirable if it can be done safely and effectively.

Methods

The authors reviewed the records of 207 patients ranging from 3 to 18 years of age with cerebral palsy who underwent placement or revision of a baclofen pump. They identified 38 patients with suspected or documented infectious complications. Initial attempts were made to eradicate infection with the devices in situ in all patients. Methods and effectiveness of pump salvage were evaluated.

Results

Of the 38 patients identified, 13 (34.2%) had documented infections; 11 had deep wound/pocket empyemas and 2 had meningitis. Eight patients with deep wound infections received intravenous antibiotics alone. All required pump explantation. The remaining 3 patients underwent a washout procedure as well; the infection was cured in 1 patient. Both patients with meningitis received intravenous and intrathecal antibiotics, and both required device explantation. In addition, 25 patients (65.8%) had excessive or increasing wound erythema. No objective criteria to document a superficial infection were present. The wounds were considered suspicious and were managed with serial examinations and oral antibiotics. The erythema resolved in 24 of the 25 patients.

Conclusions

In general, observation, wound care, and oral antibiotics are sufficient for wounds that are suspicious for superficial infection. For deep-seated infection, antibiotic therapy alone is generally insufficient and explantation is required. Washout procedures can be considered, but failures are common.

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June Yowtak, Douglas Hughes, Ian Heger and Samuel D. Macomson

A 9-year-old boy with spina bifida, Chiari II malformation, and hydrocephalus presented with signs of increased intracranial pressure consistent with a shunt malfunction. Radiological investigations revealed an intracranial calcified lesion along the ventricular catheter. A shunt tap revealed a translucent milky white fluid. The patient underwent a ventriculostomy and, eventually, a shunt revision. Pathology findings were consistent with the formation of dystrophic calcification and a pseudocyst around the shunt catheter. Postoperatively, the patient returned to his neurological baseline. This is, to the best of the authors' knowledge, the first report of an intracranial calcified pseudocyst in a patient with normal renal function.

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Khoi D. Nguyen, Haroon F. Choudhri and Samuel D. Macomson

OBJECTIVE

Peripheral nerve biopsy is a useful tool in diagnosing peripheral neuropathies. Sural and gracilis nerves have become the most common targets for nerve biopsy. However, the yield of sural nerve biopsy is limited in patients who have motor neuropathies, and gracilis nerve biopsy presents technical challenges and increased complications. The authors propose the intercostal nerve as an alternative motor nerve target for biopsy.

METHODS

A total of 4 patients with suspected peripheral neuropathies underwent intercostal nerve biopsy at the authors’ institution. A rib interspace that is inferior to the pectoralis muscle and anterior to the anterior axillary line is selected for the procedure. Generally the lower intercostal nerves (i.e., T7–11) are targeted. An incision is made over the inferior aspect of the superior rib at the chosen interspace. Blunt dissection is carried down to the neurovascular bundle and the nerve is isolated, ligated, and cut to send for pathological examination.

RESULTS

The average operative time for all cases was 73 minutes, with average blood loss of 8 ml. Biopsy results from 1 patient exhibited axonopathy, and the other 3 patients demonstrated axonopathy with demyelination. There were no short- or long-term postoperative complications. None of the patients reported sensory or motor deficits related to the biopsy at 6 weeks postoperatively.

CONCLUSIONS

The intercostal nerve can be an alternative target for biopsy, especially in patients with predominantly motor neuropathies, due to its mixed sensory and motor fibers, straightforward anatomy, minimal risk of serious sensory deficits, and no risk of motor impairment.