Spinal cord herniation: management and outcome in a series of 12 consecutive patients and review of the literature.

BACKGROUND: Spinal cord herniation is a rare entity that has been recognized and described with increasing frequency in the past few years. It is characterized by herniation of the spinal cord through an anterior dural defect. In their study of 12 cases, the authors attempt to develop management and treatment guidelines for patients suffering from this condition. METHODS: A retrospective analysis of the medical files was carried out in a series of 12 consecutive patients treated at our Institution between 1998 and 2011 for spinal cord herniation. The clinical, radiological and surgical findings, management and outcome were reviewed. RESULTS: The male:female ratio was 5:7, with a mean age of 47 years (range 26­71 years). All patients presented a progressively worsening symptomatology. Symptoms at presentation included progressive myelopathy, corticospinal tract sign, algoparesthesia and sphincter dysfunction. The radiological appearance was uniform. All the lesions were located between the T2 and T8 vertebrae. One patient was initially managed conservatively. All patients underwent surgical correction via a posterior approach, with reduction of the herniated spinal cord, the positioning of a muscular autograft to fill the anterior cavity and closure of the dural defect with an artificial dural patch. Six patients showed improvement of preoperative symptomatology at follow-up, while the others remained free from symptom progression. CONCLUSIONS: The authors present one of the largest studies to date regarding patients with spinal cord herniation and emphasize that the possibility of this condition must be kept in mind when addressing all patients with progressive myelopathy.

DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.

Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.

Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage.

CONTEXT: Neurosurgery is regarded as the first-line treatment of acromegaly. Because of its low cure rate in macro and invasive adenoma, the role of primary medical treatment is debated. OBJECTIVE: Our objective was to evaluate primary pharmacological treatment in acromegaly. DESIGN AND SETTING: We conducted an open prospective study at two Italian tertiary level centers. PATIENTS: We studied 67 consecutive patients (36 women; age, 54.9 +/- 14.2 yr; 72% bearing macroadenoma). INTERVENTION: Individually tailored octreotide LAR (OCLAR) was administered. MAIN OUTCOME MEASURES: Outcomes included safe GH (<2.5 mug/liter), normal age-matched IGF-I levels, and tumor shrinkage. RESULTS: After a median follow-up of 48 months (range, 6-108 months), safe GH levels and normal age-matched IGF-I values were obtained by 68.7 and 70.1% of patients, respectively. Hormonal endpoints were achieved regardless of basal levels, and early results were predictive of outcome. Tumor shrank in 82.1% of patients by 62 +/- 31% (range, 0-100%), decreasing from 2101 +/- 2912 to 1010 +/- 2196 mm(3) (P < 0.0001). The higher the basal GH values and the greater the GH/IGF-I changes on treatment, the greater the tumor shrinkage. Tumor disappeared in three patients and was progressively reduced to empty sella in five patients; apparent magnetic resonance imaging cavernous sinus invasion disappeared in three. In males, testosterone increased, restoring eugonadism in 64% of hypogonadal patients. CONCLUSIONS: The efficacy on GH/IGF-I levels in unselected patients and the outstanding volumetric control indicate that treatment with OCLAR may be the first therapeutic approach to all acromegalic patients not amenable to surgical cure. Tumor shrinkage might also encourage the evaluation of primary OCLAR adoption in patients with initial visual field defects.

Four-year treatment with octreotide-long-acting repeatable in 110 acromegalic patients: predictive value of short-term results?

The effects of a very prolonged treatment with octreotide (OC)-long-acting repeatable (LAR) were retrospectively evaluated in 110 patients with acromegaly, showing a GH/IGF-I decrease of at least 20% vs. baseline after a short-term (6-month) OC-LAR challenge. OC-LAR was given (20 mg, im, every 28 d for 3 injections, then individually tailored) as adjuvant treatment (AT) in 59. The other 51 [primary treatment (PT)] were naive or previously treated by pharmacotherapy. IGF-I normalized in 83 patients [75%; from 770 +/- 26 (mean +/- SE) to 276 +/- 15 micro g/liter; P < 0.0001; median follow-up, 30 months; range, 18-54 months). A progressive increase in the rate of IGF-I normalization was observed. GH fell to less than 2.5 micro g/liter in 72% and to less than 1 micro g/liter in 27% (from 20.7 +/- 2.4 to 2.2 +/- 0.2 micro g/liter; P < 0.0001). PT and AT patients achieved similar final GH/IGF-I levels and rates of normalization. Patients attaining safe GH and normal IGF-I had GH levels below 5 micro g/liter after 3 months and IGF-I levels below 550 micro g/liter after 6 months. No tachyphylaxis was observed. The up-titration to 30 mg improved IGF-I suppression. Elderly patients had greater sensitivity. Tumor shrank in 46% of assessable patients, in 77% of PT patients, and in 91% of naive patients. The powerful suppression of GH/IGF-I levels without tachyphylaxis, the finding of progressive increase in the rate of IGF-I normalization and of superimposable effects in PT and AT patients, and the predictive value of short-term results support the role of PT of acromegaly with OC-LAR in at least some patients.

Cabergoline addition to depot somatostatin analogues in resistant acromegalic patients: efficacy and lack of predictive value of prolactin status.

BACKGROUND: Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH-IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking. DESIGN: Prospective open trial. PATIENTS: In 19 acromegalic patients with active disease (34-82 years old, seven males, 12 females) resistant to chronic (9-12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved 'safe' GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 micro g/l (range 16-60 micro g/l; 1 micro g = 21.2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients. RESULTS: The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1-3.5 mg/week), decreased GH from 6.6 +/- 0.9 to 4.6 +/- 0.6 micro g/l (P = 0.018), and IGF-I from 552 +/- 44 to 428 +/- 54 micro g/l (P = 0.019) after 6 months (median, range 3-18 Months). Combined treatment decreased GH to < 2.5 micro g/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (-49 +/- 7%, and -47 +/- 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 +/- 8% in four, and IGF-I by 35-38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated. CONCLUSIONS: The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.