Effects of Two Exercise Regimes on Patients with Chiari Malformation Type 1: a Randomized Controlled Trial.

This study aims to measure the effects of two different exercise programs on neck pain, proprioception, balance, coordination, posture, and quality of life in patients with Chiari malformation (CM) type 1. Sixteen patients were randomized to two different exercise programs: a tailored exercise protocol for CM (TEP-CM) and cervical spinal stabilization exercises (CSSE). Both exercise programs were implemented by a physiotherapist 3 days a week for 6 weeks. The primary outcome was Neck Disability Index. Secondary outcomes were visual analogue scale for pain, joint position sense error measurement, Berg Balance Scale, Time Up and Go Test, International Coordination Ataxia Rating Scale, PostureScreen Mobile, and Short Form-36. Assessments were done immediately before and after the intervention programs. Both groups showed significant improvement in Neck Disability Index, and some secondary outcome measures (P < 0.05). However, there were no statistical differences in post-intervention changes between the groups (P > 0.05). This is the first study to examine the effects of different exercise programs on symptoms in patients with CM type 1. Our preliminary findings indicate that exercise programs can improve pain, balance, proprioception, posture, coordination, and quality of life in CM type 1. Therefore, exercise should be considered safe, beneficial, and low-cost treatment option for CM type 1 patients without surgical indications.

Levetiracetam treatment in an experimental model of sciatic nerve injury: A randomized controlled trial.

AIM: This study examined whether levetiracetam contributes to improvements in the axon-nerve damage in an experimental rat model. MATERIALS AND METHODS: Forty-eight Wistar albino adult male rats weighing 250-300 gr were randomized into six groups having or not having sciatic nerve damages and receiving different (none, 300 and 600 mg/kg) levetiracetam doses, and control (non-levetiracetam). Functional gait analysis and tissue sample analysis with the aid of light microscopy and hematoxylin-eosin dye were evaluated between the groups. Additionally, scanning electron microscopy (SEM) was used for the detailed examination of sciatic nerves. S-100 (Schwann cell marker) immunoreactivities in sciatic nerve was detected by immunohistochemistry. RESULTS: Sciatic functional index of the injured rats receiving 300 mg/kg levetiracetam was -65.59 ± 29.48 and -47.13 ± 21.36 in the 2nd and 6th weeks, respectively (p < 0.001). Also, IMA and TOS levels were significantly higher in the control group compared to those receiving levetiracetam (p = 0.001 and p < 0.001, respectively).      The most significant nerve regeneration was in the group injured and treated with LEV 600 mg/kg (p < 0.05). CONCLUSION: There was a significant improvement in the sciatic functional index, histopathological findings, and parameters showing tissue oxidant status in rats with sciatic nerve injury receiving levetiracetam treatment. Further investigations should be performed to evaluate the contribution of levetiracetam as a treatment modality in sciatic nerve injuries.

Idiopathic granulomatous hypophysitis mimicking adenoma.

Hypophysitis is a rare disease of pituitary gland, which, although it is usually a primary lesion, can also occur secondary to systemic conditions. Granulomatous hypophysitis is an inflammatory disease condition which accounts for less than 1% of all cellular lesions and can mimic adenoma. A 32-year-old woman presented with weight gain, galactorrhea and blurred vision. The MRI showed a cystic, nodular lesion in the intermediate lobe of the pituitary gland and the initial diagnosis was adenoma. She underwent surgery and the histopathology revealed granulomas composed of epithelioid histiocytes, multinuclear giant cells and mononuclear inflammatory cells. Inflammatory diseases of the pituitary gland are much less frequent than pituitary adenomas and idiopathic granulomatous hypophysitis is extremely rare. Histopathology and the ruling out of a systemic cause are the gold standards for its diagnosis.

Idiopathic granulomatous hypophysitis mimicking adenoma

Hypophysitis is a rare disease of pituitary gland, which, although it is usually a primary lesion, can also occur secondary to systemic conditions. Granulomatous hypophysitis is an inflammatory disease condition which accounts for less than 1% of all cellular lesions and can mimic adenoma. A 32-year-old woman presented with weight gain, galactorrhea and blurred vision. The MRI showed a cystic, nodular lesion in the intermediate lobe of the pituitary gland and the initial diagnosis was adenoma. She underwent surgery and the histopathology revealed granulomas composed of epithelioid histiocytes, multinuclear giant cells and mononuclear inflammatory cells.Inflammatory diseases of the pituitary gland are much less frequent than pituitary adenomas and idiopathic granulomatous hypophysitis is extremely rare. Histopathology and the ruling out of a systemic cause are the gold standards for its diagnosis.(AU)

La hipofisitis es una enfermedad rara de la glándula pituitaria, y a pesar de ser fundamentalmente una enfermedad primaria, puede ser también secundaria a enfermedades sistémicas. La hipofisitis granulomatosa es una enfermedad inflamatoria que representa menos del 1% de todas las lesiones celulares, y remedar al adenoma. Mujer de 32 años de edad ingresada en el hospital con aumento de peso, galactorrea y visión borrosa. La RM reflejó una lesión quística y nodular en el lóbulo intermedio de la glándula pituitaria, que fue operada con diagnóstico primario de adenoma. El examen microscópico reveló granulomas formados por histiocitos epitelioides, células gigantes multinucleares y células inflamatorias mononucleares. Las enfermedades inflamatorias de la glándula pituitaria son muy raras en comparación con los adenomas pituitarios. La hipofisitis granulomatosa idiopática es una de ellas. El criterio de referencia para este diagnóstico es realizar un examen histopatológico, y descartar una causa sistémica.(AU)

Can chlorogenic acid reduce oxidative stress and in an experimental spinal cord injury?

BACKGROUND: We aimed to investigate antioxidant and neuroprotective properties of chlorogenic acid in spinal cord injury (SCI). METHODS: Twenty-one rats were divided into three groups. Laminectomy was performed in group L (n=7), spinal cord trauma was induced in group T (n=7), and spinal cord trauma was induced and chlorogenic acid treatment was started in group C (n=7). Blood samples were collected to analyze baseline values and the 12th h, 1st day, 3rd day, and 5th day catalase, native thiol (NT), total thiol (TT), disulfide (SS), SS/TT, SS/NT, and NT/TT levels. Functional analysis with Basso-Beattie and Bresnahan scores was performed at the same time points. Total antioxidant status (TAS), total oxidative stress, oxidative stress index, and cyclooxygenase-2 (Cox-2) were examined in the spinal cord of rats euthanized on day 7; results were statistically analyzed. RESULTS: On day 7, catalase levels in Group C were significantly higher than baseline levels, whereas those in Group T were significantly lower than baseline levels; Group L showed no significant difference (p=0.008). SS values on day 7 were lower in Group T than in Groups C and L. Group C showed the lowest decrease in NT/TT level after trauma. On day 7, SS/TT level was high in Group T but stable in Groups C and L (p=0.04). Histopathological examination revealed significantly lower Cox-2 and TAS levels in Group C than in Group T (p=0.003, p=0.017, respectively). CONCLUSION: In this study, SCI was primarily examined through thiol-SS balance, and it was demonstrated by experimental models that chlorogenic acid has antioxidant and neuroprotective effects in SCI.

Effect of mesenchymal stem cells therapy in experimental kaolin induced syringomyelia model.

BACKGROUND: Syringomyelia is a pathological cavitation of the spinal cord. In this study, we examined whether a syrinx cavity would limit itself with axonal regeneration and stem cell activity in the cavity, and we evaluated subjects on a functional basis. METHODS: Groups were designated as kaolin, trauma, kaolin-trauma, and saline groups. Also divided out of the syringomyelia treated groups were those given human mesenchymal stem cells (hMSCs). All groups were evaluated with immunohistochemistry, electron microscopy, confocal microscopy and functionally. RESULTS: The kaolin-trauma group had a significant correction of BBB score with hMSCs therapy. The syrinx cavity measurements showed significant improvement in groups treated with hMSCs. The tissue surrounding the syrinx cavity, however, appeared to be better organized in groups treated with hMSCs. The process of repair and regeneration of damaged axons in the lesion were more improved in groups treated with hMSCs. Using confocal microscopy, fluorescence of hMSCs was observed in the central canal, in the ependymal tissue, and around the lesion. CONCLUSIONS: It was concluded that axonal repair accelerated in groups receiving stem cells, and thus, stem cells may be effective in recovery of neural tissue and myelin damage in syringomyelia.

The Past, Present, and Future Statuses of Formerly Classified "Atypical Pituitary Adenomas": A Clinicopathological Assessment of 101 Cases in a Cohort of More than 1,000 Pure Endoscopically Treated Patients in Single Center.

Objective This study was aimed to assess the clinical aggressiveness of pituitary neoplasms that were previously defined as atypical adenomas. Methods A total of 1,042 pituitary adenomas were included in the study and 101 of them were diagnosed as atypical adenoma. Demographic characteristics, radiological evaluations, and clinical information were obtained from a computer-based patient database. Cases were categorized as atypical or typical using the criteria listed in 2004 Classification of Tumors of Endocrine Organs. Results The cure and reoperation rates did not show any statistically significant difference between the typical and atypical adenomas. However, a higher K i -67 labeling index was found to be associated with a higher rate of reoperation ( p = 0.008) in atypical adenomas. Of note, cavernous sinus invasion or parasellar extension was found to be associated with lower cure rates in patients with atypical pituitary adenomas ( p < 0.001 and p = 0.001, respectively). Conclusion Although atypical pituitary adenomas are known to be more invasive, this study demonstrated that the reoperation and cure rates are the same for typical and atypical adenomas. Our findings advocate for omitting the use of atypical adenoma terminology based solely on pathological evaluation. As stated in the 4th edition of the World Health Organization (WHO) classification, accurate tumor subtyping, evaluation of proliferation by means of mitotic count and K i -67 labeling index, and radiological and intraoperative assessments of tumor invasion should be taken into consideration in the management of such neoplasms.

The role of bilateral inferior petrosal sinus sampling in determining the preoperative localization of ACTH-secreting pituitary microadenomas in Cushing's disease: Experience of a tertiary center.

INTRODUCTION: Bilateral inferior petrosal sinus sampling (BIPSS) is an important procedure in the diagnostic work-up of Cushing's syndrome (CS). In this study, we investigated the diagnostic performance of BIPSS in detecting the source of adrenocorticotropic hormone (ACTH) secretion in Cushing's disease (CD) without radiological evidence. METHODS: Thirty-five consecutive patients who underwent BIPSS due to ACTH-dependent CS between 2010 and 2019 in our clinic and subsequently underwent transsphenoidal surgery were included. The indication for BIPSS was biochemically proven ACTH-dependent CS but normal or ≤6 mm pituitary lesion in pituitary magnetic resonance imaging (MRI). Corticotropin releasing hormone (CRH) stimulation was applied to all patients during the BIPSS procedure. BIPSS data, MRI results, pathological findings, and follow-up results were analyzed. The diagnostic performance of BIPSS was calculated. RESULTS: A total of 35 patients, 6 (17%) males and 29 (83%) females, were included in the study. Pituitary MRI was normal in 12 (34.3%) and revealed lesions ≤ 6 mm in 23 (65.7%) patients. BIPSS lateralized the right side in 13 (37.1%) and left side in 18 (51.4%) patients, while no lateralization was observed in the remaining 4 (11.5%) patients. BIPSS showed lateralization in the same direction with pituitary adenoma in 21 (60%) patients before CRH injection and in 29 (83%) patients after CRH injection (p = 0.034). The sensitivity of the BIPSS procedure was 88%. Accurate localization of the pituitary lesion was more frequent when based on BIPSS results than on MRI (83% vs. 51%, P = 0.005). CONCLUSION: BIPSS appears to be a valuable and safe diagnostic tool in patients who are diagnosed with CD biochemically but do not have clear radiological evidence of ACTH-producing lesion.

Anti-inflammatory and antioxidative effects of genistein in a model of spinal cord injury in rats.

Background: Neurological damage from spinal cord injury (SCI) is a result of primary mechanical injury and secondary damage from oxidative stress and neuroinflammation. Although genistein has been shown to have potent antioxidant and anti-inflammatory effects in studies of brain injury, its effect on secondary damage in SCI has remained unknown. Objective: To determine effects of genistein in a model of SCI in rats. Methods: We divided 21 rats evenly into 3 groups, a control group, in which only a laminectomy was performed; a trauma group in which SCI was induced; and a genistein group in which genistein was administered subcutaneously after SCI. The rats were assessed using a Basso-Beattie and Bresnahan functional score at the 12th hour and on the 1st, 3rd, 5th, and 7th days. Biochemical analyses were conducted at the same time points to determine the serum levels of catalase, ischemia-modified albumin (IMA), disulfide (SS), total thiol (TT), native thiol (NT), disulfide/total thiol (SS/TT), and native thiol/total thiol (NT/TT). Total oxidant and antioxidant capacity, and oxidative stress index were determined in spinal cord tissue obtained on the 7th day together with immunohistochemistry for cyclooxygenase-2 levels. Result: Catalase activity on the 7th day was significantly (P = 0.001) higher in the genistein-treated rats than in other groups, and IMA levels became stable earlier (3rd day) in the genistein group. SS values were significantly (P = 0.004) lower in the genistein group. NT/TT ratio were significantly (P = 0.049) higher in the genistein-treated rats on the 7th day. Conclusion: Genistein has antioxidant, anti-inflammatory, and protective effects in a model of SCI in rats and warrants further study.

Relationship Between Vasospasm and Serum Chromogranin A Levels in an Experimental Subarachnoid Hemorrhage Model.

AIM: To analyze Chromogranin A levels on vasospasm in an experimental subarachnoid heamorrhage (SAH) model. MATERIAL AND METHODS: Sixteen Wistar Albino male rats were used in study. Two groups are formed; first was consisting of 8 rats that experimental SAH was performed on them, second group was control group that nothing was done. Animals were sacrified fourtyeight hours later subarachnoid heamorrhage was occured. Peripheral venous blood samples were taken from the experimental group before SAH formation, 15 minutes, 75 minutes after experimental SAH formation and 48 hours as peak of vasospasm. Simultaneous peripheral venous blood samples were also collected from the control group. Blood samples were biochemically evaluated after centrifugation and serum Chromogranin A levels were studied. RESULTS: Serum chromogranin A levels increased statistically significant (p < 0.05) at the 15th minute after SAH, as the samples obtained from the experimental and control groups were anticipated as a result of the statistical analysis of the data after the biochemical examinations. CONCLUSION: In all these findings, we concluded that Chromogranin A could be used as a marker for the investigation of endocrine stress in the early period of post-SAH vasospasm and it could be proved by more studies.

Endoscopic Endonasal Transsphenoidal Surgery, A Reliable Method for Treating Primary and Recurrent/Residual Craniopharyngiomas: Nine Years of Experience.

OBJECTIVE: Craniopharyngioma resection is one of the most challenging surgical procedures. Herein, we describe our extended endoscopic endonasal transsphenoidal surgery (EETS) technique, and the results of 9 years of use on primary and recurrent/residual craniopharyngiomas. METHODS: This study reviewed 28 EETSs in 25 patients with craniopharyngiomas between January 2006 and September 2015. The patients were divided into 2 groups, newly diagnosed patients (group A, n = 15), and patients having residual or recurrent tumors (group B, n = 10). There was no significant difference between the groups in terms of the largest tumor diameter (P = 0.495), and all patients underwent EETS. The clinical and ophthalmologic examinations, imaging studies, endocrinologic studies, and operative findings for these cases were reviewed retrospectively. RESULTS: The number of gross total resections in group A was 13/15, and 7/10 in group B. Three of the patients developed postoperative cerebrospinal fluid leakage (all in group A). There were no neurovascular or ophthalmologic complications, and no meningitis or mortality was observed. CONCLUSIONS: There has been a notable increase in the use of EETS in the treatment of craniopharyngiomas during the last decade. Despite its increased use in the treatment of primary craniopharyngiomas, its implementation for recurrent or residual craniopharyngiomas has been viewed with suspicion. In this study, the results have been presented separately for primary and recurrent/residual craniopharyngiomas, so that the results can be compared. Overall, EETS is a reliable and successful surgical treatment method for primary and recurrent/residual craniopharyngiomas.

The Neuroprotective Effect of Coumaric Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats.

The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of coumaric acid on spinal cord ischemia injury in rats. Rats were divided randomly into four groups of eight animals as follows: control, ischemia, ischemia + coumaric acid, and ischemia + methylprednisolone. In the control group, only a laparotomy was performed. In all other groups, the spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. Levels of malondialdehyde and nuclear respiratory factor 1 were analyzed, as were the activity of superoxide dismutase. Histopathological and immunohistochemical evaluations were performed. Neurological evaluation was performed with the Tarlov scoring system. The ischemia + coumaric acid group was compared with the ischemia group, and a significant decrease in malondialdehyde and levels was observed. Nuclear respiratory factor 1 level and superoxide dismutase activity of the ischemia + coumaric acid group were significantly higher than in the ischemia group. In histopathological samples, the ischemia + coumaric acid group is compared with the ischemia group, and there was a significant increase in numbers of normal neurons. In immunohistochemical staining, hypoxia-inducible factor-1α and NF-kappa B immunopositive neurons were significantly decreased in the ischemia + coumaric acid group compared with that in the ischemia group. The neurological deficit scores of the ischemia + coumaric acid group were significantly higher than the ischemia group at 24 h. Our results revealed for the first time that coumaric acid exhibits meaningful neuroprotective activity following ischemia-reperfusion injury of the spinal cord.

In vivo application of poly-3-hydroxyoctanoate as peripheral nerve graft.

OBJECTIVE: This study aims to investigate the degree of biocompatibility and neuroregeneration of a polymer tube, poly-3-hydroxyoctanoate (PHO) in nerve gap repair. METHODS: Forty Wistar Albino male rats were randomized into two groups: autologous nerve gap repair group and PHO tube repair group. In each group, a 10-mm right sciatic nerve defect was created and reconstructed accordingly. Neuroregeneration was studied by sciatic function index (SFI), electromyography, and immunohistochemical studies on Days 7, 21, 45 and 60 of implantation. Biocompatibility was analyzed by the capsule formation around the conduit. Biodegradation was analyzed by the molecular weight loss in vivo. RESULTS: Electrophysiological and histomorphometric assessments demonstrated neuroregeneration in both groups over time. In the experimental group, a straight alignment of the Schwann cells parallel to the axons was detected. However, autologous nerve graft seems to have a superior neuroregeneration compared to PHO grafts. Minor biodegradation was observed in PHO conduit at the end of 60 d. CONCLUSIONS: Although neuroregeneration is detected in PHO grafts with minor degradation in 60 d, autologous nerve graft is found to be superior in axonal regeneration compared to PHO nerve tube grafts. PHO conduits were found to create minor inflammatory reaction in vivo, resulting in good soft tissue response.

Aquaporin-4 expression is not elevated in mild hydrocephalus.

BACKGROUND: Aquaporin-4 (aqp-4) is a member of water channel family proteins primarily expressed in the central nervous system. Physiologically it is the main channel providing water transport into the nervous system water compartments and across the blood-brain barrier. Several studies demonstrated its compensatory role in severe hydrocephalus. However, its role is not clear during the initial stages of hydrocephalus. OBJECTIVE: This study was designed to investigate aqp-4 expression in less severe forms of hydrocephalus and to determine its role in disease progression. METHODS: Twenty-five male Wistar-Hannover rats, were distributed into experimental (n = 20) and control (n = 5) groups. Hydrocephalus was induced in the experimental group by injection of 5 µl 25% kaolin suspension into the cisterna magna. Control animals received an injection of 5 µl normal saline. Eight weeks later, the animals were killed by the perfusion-fixation method. Immunohistochemical and Western blot analysis were performed. RESULTS: Ventricular dilatations were noted in all experimental animals. Both groups demonstrated positive immunoreactive signals to aqp-4. Immunohistochemically there were no changes in aqp-4 pattern and expression intensity between experimental and control animals. Similarly, Western blot analysis revealed mean aqp-4 values in experimental and control groups as 0.3436 and 0.3917, respectively, and the difference did not reach statistical significance (p > 0.05). CONCLUSION: Our results indicate that aqp-4 is not up-regulated during the initial stages of hydrocephalus. This implies that aqp-4 may not play a significant role in hydrocephalus compensation until severe ventricular dilatation occurs.

Expression of water channel aquaporin-4 during experimental syringomyelia: laboratory investigation.

OBJECT: Aquaporins (aqp) are protein channels providing water transport across cell membranes. The main member of this family expressed in the CNS is aqp-4. The pattern and amount of expression of this channel suggest a dominant role in bulk water movement into the nervous tissue. It has also been shown to play a role in several water balance disorders in the CNS. In this study, the authors investigated the possible role of aqp-4 in syringomyelia. METHODS: Twenty-five male Wistar-Hannover rats were divided into experimental (20 rats) and control (5 rats) groups. Syringomyelia was induced in the experimental group by kaolin injection into the cisterna magna. Eight weeks later, the animals were killed, and their spinal cords were removed. Central canal dilations were noted in all experimental animals. Immunohistochemistry and Western blot analysis were performed to evaluate aqp-4 expression. RESULTS: Both groups demonstrated positive immunoreactive signals to aqp-4. Western blot analysis revealed a slight decrease in the mean aqp-4 value in the experimental group; however, the difference did not reach statistical significance (p > 0.05). Immunohistochemical analysis showed a similar pattern and intensity of aqp-4 staining in both groups. CONCLUSIONS: The results of this study indicate that aqp-4 most likely does not play a major role in chronic syringomyelia. Its slight downregulation during the initial stage of syrinx formation is possibly a compensatory mechanism. This effect is not present during the late stage of syringomyelia, and aqp-4 is most likely not involved in the pathophysiology of syrinx cavity formation.

Pineal cyst apoplexy: report of an unusual case managed conservatively.

Pineal cyst apoplexy is a very rare entity with previously reported symptoms of severe frontal or occipital headache, gaze paresis and visual field defects, nausea or vomiting, syncope, ataxia, hearing loss and sudden death. The treatment options for symptomatic pineal cysts are observation, shunting, aspiration via stereotactic guidance or endoscopy, third ventriculostomy, ventriculocysternostomy, and/or surgical resection by craniotomy and microsurgery. Here, the authors report an unusual case of a 28-year-old male patient with pineal cyst apoplexy, presenting with headache, insomnia, and sexual dysfunction symptoms who is being managed conservatively and observed for two years by an academic tertiary care unit.