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Issam A. Awad

✓ In this paper the author recounts an anecdote presented by Galen of Pergamum (circa 130–200 A.D.) about a sophist named Pausanias, who fell from his mount and struck his back against a rock. The patient developed a subsequent loss of sensation in the fingers of his left hand with complete sparing of motor function. Numerous medications were applied to his hand but to no avail. Galen stated that he applied the same medications to the original point of dorsal tenderness, resulting in the patient's dramatic and full recovery. Galen attributed the healing to local drug action at the site of a presumed spinal root injury, at the level of C-7. Galen repeated this anecdote elsewhere to illustrate the remote effects of spinal cord and nerve injury and the importance of treating the site of pathology, rather than its somatic manifestations. Galen's observation is interpreted in light of his earlier experiments on spinal cord and nerve transections in live animals and his evolving concepts of functional and correlative neuroanatomy. This anecdote is also discussed as a striking example of the dangers of conjecture and the temptation to confuse association with causation when interpreting the effects of therapy in light of widely accepted paradigms.

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Cavernous angiomas: deconstructing a neurosurgical disease

JNSPG 75th Anniversary Invited Review Article

Issam A. Awad and Sean P. Polster

Cavernous angioma (CA) is also known as cavernoma, cavernous hemangioma, and cerebral cavernous malformation (CCM) (National Library of Medicine Medical Subject heading unique ID D006392). In its sporadic form, CA occurs as a solitary hemorrhagic vascular lesion or as clustered lesions associated with a developmental venous anomaly. In its autosomal dominant familial form (Online Mendelian Inheritance in Man #116860), CA is caused by a heterozygous germline loss-of-function mutation in one of three genes—CCM1/KRIT1, CCM2/Malcavernin, and CCM3/PDCD10—causing multifocal lesions throughout the brain and spinal cord.

In this paper, the authors review the cardinal features of CA’s disease pathology and clinical radiological features. They summarize key aspects of CA’s natural history and broad elements of evidence-based management guidelines, including surgery. The authors also discuss evidence of similar genetic defects in sporadic and familial lesions, consequences of CCM gene loss in different tissues at various stages of development, and implications regarding the pathobiology of CAs.

The concept of CA with symptomatic hemorrhage (CASH) is presented as well as its relevance to clinical care and research in the field. Pathobiological mechanisms related to CA include inflammation and immune-mediated processes, angiogenesis and vascular permeability, microbiome driven factors, and lesional anticoagulant domains. These mechanisms have motivated the development of imaging and plasma biomarkers of relevant disease behavior and promising therapeutic targets.

The spectrum of discoveries about CA and their implications endorse CA as a paradigm for deconstructing a neurosurgical disease.

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Issam A. Awad and Gene H. Barnett

✓ The mechanism of nonhemorrhagic neurological deterioration from spinal arteriovenous malformation (AVM) and the role of acute surgical intervention in this setting are not well understood. The case is described of a 65-year-old man who presented with a 2-year history of mild gait spasticity and vague sensory complaints affecting both lower extremities. Following a diagnostic lumbar puncture, these symptoms progressed painlessly over a 4-day period to total motor paraplegia, urinary retention, and hypesthesia in all modalities with a midthoracic sensory level. Magnetic resonance imaging showed a probable spinal AVM but no evidence of hemorrhage or cord compression. Spinal angiography confirmed the diagnosis of spinal AVM fed by radicular branches of left T-7 and T-8 segmental intercostal arteries. Drainage was via long dorsal veins caudally. Emergency laminectomy with intradural exploration was performed. There was no evidence of prior hemorrhage or focal mass effect, although the cerebrospinal fluid pressure was elevated. The dural component of the spinal AVM was excised, and its communications with the spinal cord were disconnected intradurally. Neurological function started improving within 6 hours of the patient awakening from anesthesia. He had achieved antigravity strength in every muscle group of the lower extremities by the time of discharge to a rehabilitation center 10 days after surgery. Three months postoperatively, he was ambulating with a walker and was continent of urine and stool. Possible pathophysiological mechanisms are discussed in light of the favorable response to timely surgical intervention.

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Issam A. Awad, Javad Hekmatpanah, and David Frim

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John R. Robinson, Issam A. Awad, and John R. Little

✓ The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma.

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John R. Little, Issam A. Awad, Stephen C. Jones, and Zeyd Y. Ebrahim

✓ This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (± standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 ± 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 ± 0.6 torr. Mean CO2 reactivity was 1.1 ± 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 ± 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.