Muscle biopsies of patients with immune-mediated inflammatory myopathies are characterized by a c... more Muscle biopsies of patients with immune-mediated inflammatory myopathies are characterized by a combination of chronic inflammatory infiltrates and muscle fiber necrosis. In addition, there are typical histochemical, immunohistochemical, and ultrastructural findings of each type of inflammatory myopathy. Accurate classification of inflammatory myopathies is important because inclusion body myositis does not respond to immunosuppressive treatment, polymyositis is frequently part of an overlap syndrome, and dermatomyositis is associated with cancer in adults. Necrotizing myopathy without inflammation may be due to a partially treated inflammatory myopathy, a toxic myopathy, or a paraneoplastic myopathy. Metabolic myopathies and muscular dystrophies may clinically and rarely pathologically mimic inflammatory myopathy. Correct identification of these entities depends on better awareness of clinical similarities between metabolic myopathy and inflammatory myopathy; appropriate utilization of immunohistochemical, ultrastructural, biochemical, and genetic techniques on muscle samples in difficult cases; and maximizing communication between the clinician and the pathologist.
The laminar patterns displayed by MR microscopy (MRM) form one basis for the classification of th... more The laminar patterns displayed by MR microscopy (MRM) form one basis for the classification of the cytoarchitectonic areas (Brodmann areas). It is plausible that in the future MRM may depict Brodmann areas directly, and not only by inference from gross anatomic location. Our purpose was to depict the laminar cytoarchitecture of excised, formalin-fixed specimens of human cerebral cortex by use of 9.4-T MR and to correlate MR images with histologic stains of the same sections. Formalin-fixed samples of human sensory isocortex (calcarine, Heschl's, and somatosensory cortices), motor isocortex (hand motor area of M1), polar isocortex (frontal pole), allocortex (hippocampal formation), and transitional periallocortex (retrosplenial cortex) were studied by MRM at 9.4 T with intermediate-weighted pulse sequences for a total overnight acquisition time of 14 hours 17 minutes for each specimen. The same samples were then histologically analyzed to confirm the MR identification of the cort...
Hernia : the journal of hernias and abdominal wall surgery, 2008
Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We repor... more Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.
Magnetic resonance imaging clinics of North America, 2003
MR microscopy at 9.4T depicts the architecture of the brain in exquisite detail, including the in... more MR microscopy at 9.4T depicts the architecture of the brain in exquisite detail, including the individual laminae of the cortex, the individual nuclei of the basal ganglia, the thalami, subthalami and metathalami, and the orientations and relationship among the dominant nuclei and white matter tracts of the brain. The authors believe that these anatomic relations will ultimately be displayed in vivo as clinical MR scanners begin to operate at field strengths of 4.7T, 7T, and 8T. Then, those familiar with this anatomy will be able to interpret patient images with far greater sophistication.
Acromegaly is associated with serious morbidity and mortality, if not well controlled. Approved s... more Acromegaly is associated with serious morbidity and mortality, if not well controlled. Approved somatostatin receptor ligands (SRLs) are a mainstay of medical therapy and exhibit preferential affinity for somatostatin receptor (SSTR) subtype 2. Our objective was to assess whether characteristic features of individual growth hormone (GH)-secreting adenomas at diagnosis, correlated with SRL sensitivity, using defined tumor markers. A retrospective review of 86 consecutive acromegaly surgeries (70 patients) performed between January 2006 and December 2011 was undertaken. Patients with any preoperative medical treatment were excluded. Response to SRL therapy was defined as normalization of insulin-like growth factor 1 (IGF1) and random GH < 1.0 ng/dl. Immunohistochemical staining pattern: sparsely granulated, densely granulated, mixed growth hormone-prolactin (GH/PRL) and SSRT2 positivity (+) were correlated with clinicopathologic features, adenoma recurrence, and SRL treatment response. Two-tailed t test, univariate ANOVA, Kruskal-Wallis and bivariate correlation were performed using PAWS 18. The cohort eligible for analysis comprised 59 patients (41 female and 18 male). Based on pre-surgery adenoma imaging dimensions, 81.3% (48) were macroadenomas and average maximum tumor diameter was 18.1 ± 9.9 mm. Patients on SRLs were followed for 13.4 ± 15.8 (mean ± SD) months. Sparsely granulated adenomas were significantly larger at diagnosis, exhibited lower SSTR2 positivity and had a lower rate of biochemical normalization to SRLs. Densely granulated adenomas were highly responsive to SRLs. Overall, patients with SSTR2A+ adenomas responded more favorably to SRL treatment than those with SSTR2A- adenomas. Eighty-one percent of patients with SSTR2A+ adenomas were biochemically controlled (both GH and IGF1) on SRL treatment, e.g. a much higher normalization rate than that reported in the unselected acromegaly population (20-30%). Detailed knowledge of adenoma GH granularity and the immunohistochemical SSTR2A+ status is a predictor of SRL response. These immunoreactive markers should be assessed routinely on surgical specimens to assess subsequent SRL responsiveness and potential need for adjunctive therapy after surgery.
Biochemical and Biophysical Research Communications, 2014
Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the under... more Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the understanding of molecular mechanisms driving this process is nascent. In this study, we examined the secretory chemokine profile of medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned media (CM) of meningothelial cells increased adhesion, spreading and migration of medulloblastoma. VEGFA was identified at elevated levels in the CM from BMEN1 cells (as compared to DAOY CM); however, recombinant VEGFA alone was insufficient to enhance medulloblastoma cell migration. In addition, bevacizumab, the VEGFA scavenging monoclonal antibody, did not block the migratory phenotype induced by the CM. These results reveal that paracrine factors secreted by meningothelial cells can influence migration and adherence of medulloblastoma tumor cells, but VEGFA may not be a specific target for therapeutic intervention in this context.
Journal of Neurological Surgery Part B: Skull Base, 2013
Objectives To analyze surgical outcomes and predictive factors of disease remission in acromegaly... more Objectives To analyze surgical outcomes and predictive factors of disease remission in acromegaly patients who underwent microscopic transsphenoidal surgery (TSS) for a growth hormone (GH)-secreting adenoma. Design A 6-year retrospective review of 86 consecutive acromegaly surgeries. Setting Procedures performed at a single institution by a single surgeon. Participants Seventy acromegaly patients. Main Outcome Measures Demographic information, preoperative laboratory values, tumor imaging data, and morphological and immunohistochemical data were collected. Predictive values using the latest and most stringent biochemical remission criteria were determined using univariate and multivariate statistical analyses. Results Remission rate for 59 (18 males) acromegaly patients meeting the study inclusion criteria was 52.5%. Remission rates for micro- and macroadenomas were 81.8% and 45.8%, respectively. Patients of older age, with a smaller tumor, lower Knosp grade, lower preoperative GH, and insulinlike growth factor 1 levels were more likely to achieve remission. Remission rate decreased significantly with repeat surgeries. Those patients with adenomas that stained positive for somatostatin receptor subtype 2A were less likely to experience tumor recurrence and more likely to respond to medical treatment with persistent or elevated GH hypersecretion. Conclusions Microscopic TSS continues to be a viable means for treating acromegaly patients. Patients should be followed long term.
Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal... more Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model. HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression. Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immun...
Postoperative serum cortisol is used as an indicator of Cushing&a... more Postoperative serum cortisol is used as an indicator of Cushing's disease (CD) remission following transsphenoidal surgery (TSS) and guides (controversially) the need for immediate adjuvant treatment for CD. We investigated postoperative cortisol and adrenocorticotropic hormone (ACTH) levels as predictors of remission/recurrence in CD in a large retrospective cohort of patients with pathologically confirmed CD, over 6 years at a single institution. Midnight and morning cortisol, and ACTH at 24-48 h postoperatively (>24 h after last hydrocortisone dose) were measured. Remission was defined as normal 24-h urine free cortisol, normal midnight salivary cortisol, a normal dexamethasone-corticotropin releasing hormone (CRH) test or continued need for hydrocortisone, assessed periodically. Statistical analysis was performed using PASW 18. Follow up data was available for 52 patients (38 females and 14 males), median follow up was 16.5 month (range 2-143 months), median age was 45 years (range 21-72 years), 28 tumors were microadenomas and 16 were macroadenomas, and in eight cases no tumor was observed on magnetic resonance imaging. No patient with postoperative cortisol levels >10 mcg/dl were found to be in remission. Ten of the 52 patients with cortisol >10 mcg/dl by postoperative day 1-2 underwent a second TSS within 7 days. Forty-three patients (82.7%) achieved CD remission (36 after one TSS and 7 after a second early TSS) and six patients suffered disease recurrence (mean 39.2 ± 52.4 months). An immediate second TSS induced additional hormonal deficiencies (diabetes insipidus) in three patients with no surgical complications. Persistent disease was noted in nine patients despite three patients having an immediate second TSS. Positive predictive value for remission of cortisol <2 mcg/dl and ACTH <5 pg/ml was 100%. Cortisol and ACTH levels (at all postoperative time points and at 2 months) were correlated (r = 0.37, P < 0.001). Nadir serum cortisol of ≤2 mcg/dl and ACTH <5 pg/ml predicted remission (P < 0.005), but no level predicted lack of recurrence. Immediate postoperative ACTH/cortisol did not predict length of remission. No patients with postoperative cortisol >10 mcg/dl were observed to have delayed remission; all required additional treatment. There was no significant difference in age, body mass index, tumor size and length of follow-up between postoperative cortisol groups: cortisol ≤2 mcg/dl, cortisol >5 mcg/dl and cortisol >10 mcg/dl. Immediate postoperative cortisol levels should routinely be obtained in CD patients post TSS, until better tools to identify early remission are available. Immediate repeat TSS could be beneficial in patients with cortisol >10 mcg/dl and positive CD pathology: our combined (micro- and macroadenomas) remission rate with this approach was 82.7%. ACTH measurements correlate well with cortisol. However, because no single cortisol or ACTH cutoff value excludes all recurrences, patients require long-term clinical and biochemical follow-up. Further research is needed in this area.
Cavernous malformations (CMs) of the optic pathway and hypothalamus (OPH) are extremely rare. Pat... more Cavernous malformations (CMs) of the optic pathway and hypothalamus (OPH) are extremely rare. Patients with these lesions typically present with chiasmal apoplexy, characterized by sudden visual loss, acute headaches, retroorbital pain, and nausea. Surgical removal is the recommended treatment to restore or preserve vision and to eliminate the risk of future hemorrhage. However, the anatomical location and eloquence of nearby neural structures can make these lesions difficult to access and remove. In this study, the authors review the literature for reported cases of OPH CMs to analyze clinical and radiographic presentations as well as surgical approaches and neurological outcomes. A MEDLINE/PubMed search was performed, revealing 64 cases of OPH CMs. The authors report an additional case in the study, making a total of 65 cases. Each case was analyzed for clinical presentation, lesion location, radiographic features, treatment method, and visual outcome. In 65 patients with OPH CMs, the optic chiasm was affected in 54 cases, the optic nerve(s) in 35, the optic tract in 13, and the hypothalamus in 5. Loss of visual field and acuity was the most common presenting symptom (98%), followed by headache (60%). The onset of symptoms was acute in 58% of patients, subacute in 15%, and chronic progressive in 26%. Computed tomography scans revealed hyperdense suprasellar lesions, with calcification visible in 56% of cases. Magnetic resonance imaging typically demonstrated a heterogeneous lesion with mixed signal intensities suggestive of blood of different ages. The lesion was often surrounded by a peripheral rim of hypointensity on T2-weighted images in 60% of cases. Minimal or no enhancement occurred after the administration of gadolinium. Hemorrhage was reported in 82% of cases. Most patients were surgically treated (97%) using gross-total resection (60%), subtotal resection (6%), biopsy procedure alone (6%), biopsy procedure with decompression (23%), and biopsy procedure followed by radiation (2%). Those patients who underwent gross-total resection had the highest rate of visual improvement (85%). Two patients were treated conservatively, resulting in complete blindness in 1 patient and spontaneous recovery of vision in the other patient. Cavernous malformations of the OPH are rare and challenging lesions. Gross-total resection of these lesions is associated with favorable visual outcomes. Emergent surgery is warranted in patients presenting with chiasmal apoplexy to prevent permanent damage to the visual pathway.
Muscle biopsies of patients with immune-mediated inflammatory myopathies are characterized by a c... more Muscle biopsies of patients with immune-mediated inflammatory myopathies are characterized by a combination of chronic inflammatory infiltrates and muscle fiber necrosis. In addition, there are typical histochemical, immunohistochemical, and ultrastructural findings of each type of inflammatory myopathy. Accurate classification of inflammatory myopathies is important because inclusion body myositis does not respond to immunosuppressive treatment, polymyositis is frequently part of an overlap syndrome, and dermatomyositis is associated with cancer in adults. Necrotizing myopathy without inflammation may be due to a partially treated inflammatory myopathy, a toxic myopathy, or a paraneoplastic myopathy. Metabolic myopathies and muscular dystrophies may clinically and rarely pathologically mimic inflammatory myopathy. Correct identification of these entities depends on better awareness of clinical similarities between metabolic myopathy and inflammatory myopathy; appropriate utilization of immunohistochemical, ultrastructural, biochemical, and genetic techniques on muscle samples in difficult cases; and maximizing communication between the clinician and the pathologist.
The laminar patterns displayed by MR microscopy (MRM) form one basis for the classification of th... more The laminar patterns displayed by MR microscopy (MRM) form one basis for the classification of the cytoarchitectonic areas (Brodmann areas). It is plausible that in the future MRM may depict Brodmann areas directly, and not only by inference from gross anatomic location. Our purpose was to depict the laminar cytoarchitecture of excised, formalin-fixed specimens of human cerebral cortex by use of 9.4-T MR and to correlate MR images with histologic stains of the same sections. Formalin-fixed samples of human sensory isocortex (calcarine, Heschl's, and somatosensory cortices), motor isocortex (hand motor area of M1), polar isocortex (frontal pole), allocortex (hippocampal formation), and transitional periallocortex (retrosplenial cortex) were studied by MRM at 9.4 T with intermediate-weighted pulse sequences for a total overnight acquisition time of 14 hours 17 minutes for each specimen. The same samples were then histologically analyzed to confirm the MR identification of the cort...
Hernia : the journal of hernias and abdominal wall surgery, 2008
Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We repor... more Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.
Magnetic resonance imaging clinics of North America, 2003
MR microscopy at 9.4T depicts the architecture of the brain in exquisite detail, including the in... more MR microscopy at 9.4T depicts the architecture of the brain in exquisite detail, including the individual laminae of the cortex, the individual nuclei of the basal ganglia, the thalami, subthalami and metathalami, and the orientations and relationship among the dominant nuclei and white matter tracts of the brain. The authors believe that these anatomic relations will ultimately be displayed in vivo as clinical MR scanners begin to operate at field strengths of 4.7T, 7T, and 8T. Then, those familiar with this anatomy will be able to interpret patient images with far greater sophistication.
Acromegaly is associated with serious morbidity and mortality, if not well controlled. Approved s... more Acromegaly is associated with serious morbidity and mortality, if not well controlled. Approved somatostatin receptor ligands (SRLs) are a mainstay of medical therapy and exhibit preferential affinity for somatostatin receptor (SSTR) subtype 2. Our objective was to assess whether characteristic features of individual growth hormone (GH)-secreting adenomas at diagnosis, correlated with SRL sensitivity, using defined tumor markers. A retrospective review of 86 consecutive acromegaly surgeries (70 patients) performed between January 2006 and December 2011 was undertaken. Patients with any preoperative medical treatment were excluded. Response to SRL therapy was defined as normalization of insulin-like growth factor 1 (IGF1) and random GH < 1.0 ng/dl. Immunohistochemical staining pattern: sparsely granulated, densely granulated, mixed growth hormone-prolactin (GH/PRL) and SSRT2 positivity (+) were correlated with clinicopathologic features, adenoma recurrence, and SRL treatment response. Two-tailed t test, univariate ANOVA, Kruskal-Wallis and bivariate correlation were performed using PAWS 18. The cohort eligible for analysis comprised 59 patients (41 female and 18 male). Based on pre-surgery adenoma imaging dimensions, 81.3% (48) were macroadenomas and average maximum tumor diameter was 18.1 ± 9.9 mm. Patients on SRLs were followed for 13.4 ± 15.8 (mean ± SD) months. Sparsely granulated adenomas were significantly larger at diagnosis, exhibited lower SSTR2 positivity and had a lower rate of biochemical normalization to SRLs. Densely granulated adenomas were highly responsive to SRLs. Overall, patients with SSTR2A+ adenomas responded more favorably to SRL treatment than those with SSTR2A- adenomas. Eighty-one percent of patients with SSTR2A+ adenomas were biochemically controlled (both GH and IGF1) on SRL treatment, e.g. a much higher normalization rate than that reported in the unselected acromegaly population (20-30%). Detailed knowledge of adenoma GH granularity and the immunohistochemical SSTR2A+ status is a predictor of SRL response. These immunoreactive markers should be assessed routinely on surgical specimens to assess subsequent SRL responsiveness and potential need for adjunctive therapy after surgery.
Biochemical and Biophysical Research Communications, 2014
Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the under... more Leptomeningeal metastasis is a cause of morbidity and mortality in medulloblastoma, but the understanding of molecular mechanisms driving this process is nascent. In this study, we examined the secretory chemokine profile of medulloblastoma cells (DAOY) and a meningothelial cell line (BMEN1). Conditioned media (CM) of meningothelial cells increased adhesion, spreading and migration of medulloblastoma. VEGFA was identified at elevated levels in the CM from BMEN1 cells (as compared to DAOY CM); however, recombinant VEGFA alone was insufficient to enhance medulloblastoma cell migration. In addition, bevacizumab, the VEGFA scavenging monoclonal antibody, did not block the migratory phenotype induced by the CM. These results reveal that paracrine factors secreted by meningothelial cells can influence migration and adherence of medulloblastoma tumor cells, but VEGFA may not be a specific target for therapeutic intervention in this context.
Journal of Neurological Surgery Part B: Skull Base, 2013
Objectives To analyze surgical outcomes and predictive factors of disease remission in acromegaly... more Objectives To analyze surgical outcomes and predictive factors of disease remission in acromegaly patients who underwent microscopic transsphenoidal surgery (TSS) for a growth hormone (GH)-secreting adenoma. Design A 6-year retrospective review of 86 consecutive acromegaly surgeries. Setting Procedures performed at a single institution by a single surgeon. Participants Seventy acromegaly patients. Main Outcome Measures Demographic information, preoperative laboratory values, tumor imaging data, and morphological and immunohistochemical data were collected. Predictive values using the latest and most stringent biochemical remission criteria were determined using univariate and multivariate statistical analyses. Results Remission rate for 59 (18 males) acromegaly patients meeting the study inclusion criteria was 52.5%. Remission rates for micro- and macroadenomas were 81.8% and 45.8%, respectively. Patients of older age, with a smaller tumor, lower Knosp grade, lower preoperative GH, and insulinlike growth factor 1 levels were more likely to achieve remission. Remission rate decreased significantly with repeat surgeries. Those patients with adenomas that stained positive for somatostatin receptor subtype 2A were less likely to experience tumor recurrence and more likely to respond to medical treatment with persistent or elevated GH hypersecretion. Conclusions Microscopic TSS continues to be a viable means for treating acromegaly patients. Patients should be followed long term.
Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal... more Infantile and late-infantile neuronal ceroid lipofuscinoses (NCLs) are invariably fatal lysosomal storage diseases associated with defects in lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT-1) or tripeptidyl peptidase 1 (TPP1) activity. Previous preclinical studies have demonstrated that human CNS stem cells (HuCNS-SCs) produce both PPT-1 and TPP1 and result in donor cell engraftment and reduced accumulation of storage material in the brain when tested in an NCL mouse model. HuCNS-SC transplantation was tested in an open-label dose-escalation Phase I clinical trial as a potential treatment for infantile and late-infantile NCL. Study design included direct neurosurgical transplantation of allogeneic HuCNS-SCs into the cerebral hemispheres and lateral ventricles accompanied by 12 months of immunosuppression. Six children with either the infantile or late-infantile forms of NCL underwent low- (3 patients) and high- (3 patients) dose transplantation of HuCNS-SCs followed by immun...
Postoperative serum cortisol is used as an indicator of Cushing&a... more Postoperative serum cortisol is used as an indicator of Cushing's disease (CD) remission following transsphenoidal surgery (TSS) and guides (controversially) the need for immediate adjuvant treatment for CD. We investigated postoperative cortisol and adrenocorticotropic hormone (ACTH) levels as predictors of remission/recurrence in CD in a large retrospective cohort of patients with pathologically confirmed CD, over 6 years at a single institution. Midnight and morning cortisol, and ACTH at 24-48 h postoperatively (>24 h after last hydrocortisone dose) were measured. Remission was defined as normal 24-h urine free cortisol, normal midnight salivary cortisol, a normal dexamethasone-corticotropin releasing hormone (CRH) test or continued need for hydrocortisone, assessed periodically. Statistical analysis was performed using PASW 18. Follow up data was available for 52 patients (38 females and 14 males), median follow up was 16.5 month (range 2-143 months), median age was 45 years (range 21-72 years), 28 tumors were microadenomas and 16 were macroadenomas, and in eight cases no tumor was observed on magnetic resonance imaging. No patient with postoperative cortisol levels >10 mcg/dl were found to be in remission. Ten of the 52 patients with cortisol >10 mcg/dl by postoperative day 1-2 underwent a second TSS within 7 days. Forty-three patients (82.7%) achieved CD remission (36 after one TSS and 7 after a second early TSS) and six patients suffered disease recurrence (mean 39.2 ± 52.4 months). An immediate second TSS induced additional hormonal deficiencies (diabetes insipidus) in three patients with no surgical complications. Persistent disease was noted in nine patients despite three patients having an immediate second TSS. Positive predictive value for remission of cortisol <2 mcg/dl and ACTH <5 pg/ml was 100%. Cortisol and ACTH levels (at all postoperative time points and at 2 months) were correlated (r = 0.37, P < 0.001). Nadir serum cortisol of ≤2 mcg/dl and ACTH <5 pg/ml predicted remission (P < 0.005), but no level predicted lack of recurrence. Immediate postoperative ACTH/cortisol did not predict length of remission. No patients with postoperative cortisol >10 mcg/dl were observed to have delayed remission; all required additional treatment. There was no significant difference in age, body mass index, tumor size and length of follow-up between postoperative cortisol groups: cortisol ≤2 mcg/dl, cortisol >5 mcg/dl and cortisol >10 mcg/dl. Immediate postoperative cortisol levels should routinely be obtained in CD patients post TSS, until better tools to identify early remission are available. Immediate repeat TSS could be beneficial in patients with cortisol >10 mcg/dl and positive CD pathology: our combined (micro- and macroadenomas) remission rate with this approach was 82.7%. ACTH measurements correlate well with cortisol. However, because no single cortisol or ACTH cutoff value excludes all recurrences, patients require long-term clinical and biochemical follow-up. Further research is needed in this area.
Cavernous malformations (CMs) of the optic pathway and hypothalamus (OPH) are extremely rare. Pat... more Cavernous malformations (CMs) of the optic pathway and hypothalamus (OPH) are extremely rare. Patients with these lesions typically present with chiasmal apoplexy, characterized by sudden visual loss, acute headaches, retroorbital pain, and nausea. Surgical removal is the recommended treatment to restore or preserve vision and to eliminate the risk of future hemorrhage. However, the anatomical location and eloquence of nearby neural structures can make these lesions difficult to access and remove. In this study, the authors review the literature for reported cases of OPH CMs to analyze clinical and radiographic presentations as well as surgical approaches and neurological outcomes. A MEDLINE/PubMed search was performed, revealing 64 cases of OPH CMs. The authors report an additional case in the study, making a total of 65 cases. Each case was analyzed for clinical presentation, lesion location, radiographic features, treatment method, and visual outcome. In 65 patients with OPH CMs, the optic chiasm was affected in 54 cases, the optic nerve(s) in 35, the optic tract in 13, and the hypothalamus in 5. Loss of visual field and acuity was the most common presenting symptom (98%), followed by headache (60%). The onset of symptoms was acute in 58% of patients, subacute in 15%, and chronic progressive in 26%. Computed tomography scans revealed hyperdense suprasellar lesions, with calcification visible in 56% of cases. Magnetic resonance imaging typically demonstrated a heterogeneous lesion with mixed signal intensities suggestive of blood of different ages. The lesion was often surrounded by a peripheral rim of hypointensity on T2-weighted images in 60% of cases. Minimal or no enhancement occurred after the administration of gadolinium. Hemorrhage was reported in 82% of cases. Most patients were surgically treated (97%) using gross-total resection (60%), subtotal resection (6%), biopsy procedure alone (6%), biopsy procedure with decompression (23%), and biopsy procedure followed by radiation (2%). Those patients who underwent gross-total resection had the highest rate of visual improvement (85%). Two patients were treated conservatively, resulting in complete blindness in 1 patient and spontaneous recovery of vision in the other patient. Cavernous malformations of the OPH are rare and challenging lesions. Gross-total resection of these lesions is associated with favorable visual outcomes. Emergent surgery is warranted in patients presenting with chiasmal apoplexy to prevent permanent damage to the visual pathway.
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Papers by Sakir Gultekin