Erratum to "Basal Cell Carcinoma Pathology Requests and Reports Are Lacking Important Information".

[This corrects the article DOI: 10.1155/2019/4876309.].

Cervical Discogenic Pain Treatment with Percutaneous Jellified Ethanol: Preliminary Experience.

BACKGROUND: Percutaneous DiscoGel® (Gelscom SAS, France), introduced in 2007 as a promising new minimal invasive technique, showed efficacy and safety in lumbar spine surgery, with limited use and scientific reports with regard to the cervical spine. Since the first publication of its use on the cervical spine (2010), less than 100 cases have been published. We introduce an initial experience with this relatively new procedure. We hypothesized that percutaneous DiscoGel® is a safe and effective option for chronic neck pain of cervical discogenic origin. METHOD: This was a clinical study on 10 patients with chronic discogenic pain operated on for 18 cervical discs with percutaneous DiscoGel®. Inclusion criteria were patients with chronic axial or referred neck pain with MRI showing a cervical disc that is consistent with patient symptoms and failed conservative treatment. Exclusion criteria were clinical myelopathy, motor deficit, severe stenosis or reduced disc height by more than 50%, or previous cervical spine surgery. RESULTS: A total of 10 cases consisting of 6 females and 4 males underwent treatment with percutaneous DiscoGel® for 18 cervical discs. C5/C6 was the most affected level. The mean preoperative VAS score was 8; the postoperative VAS scores at 6 weeks and 3 months were 2.2 and 2.9, respectively. There were no postoperative complications or neurological deficits. CONCLUSION: The present study has the limitation of the small number of cases; however, with the limited number of studies and less than 100 published cases in the literature, this initial work shows that cervical percutaneous DiscoGel® is an effective minimally invasive bridging option between conservative and open surgical treatment for cervical discogenic pain, with a high success rate. The differentiation of pain types (nociceptive, referred, radicular, and trapezius myalgia) that can coexist is crucial for procedure selection and improving treatment outcome.

Basal Cell Carcinoma Pathology Requests and Reports Are Lacking Important Information.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common cancer affecting humans. Luckily it has negligible risk for metastasis; however it can be locally destructive to surrounding tissue. The diagnosis of this tumor relies on clinical and dermoscopic features; however confirmation requires biopsy and histologic examination. Based on clinical and pathologic findings, BCC is classified as low or high risk subtype. The clinician requesting pathology examination for BCC should provide the pathologist with detailed information including patient details, relevant clinical and medical history, site and type of the biopsy, and whether this is a primary or recurrent lesion. The pathologist on the other hand should write an adequate report containing a minimum of core set of parameters including type of BCC, depth of invasion, presence of lymphovascular or perineural invasion, and the excision margins. OBJECTIVES: The objective of this study is to evaluate whether requests by clinicians and pathology reports of BCC are adequate. METHODS: This is a retrospective analysis done at the dermatology department, faculty of medicine at Jordan University of Science and Technology, Irbid, Jordan. Reports for the period from January 2003 to December 2017 were retrieved and analyzed for data completeness. RESULTS: Most clinical request forms of BCC provided by clinicians are inadequate and lack important relevant information especially in regard to lesion history, patient medical history, and whether BCC is a primary or a recurrent one. Pathology reports for BCC cases also have significant deficiency especially in describing the histologic subtype, depth of invasion, and presence of lymphovascular and perineural invasion. However, the tumor excision margins are adequately described in almost all reports. CONCLUSIONS: The study shows that clinicians do not provide adequate clinical information when submitting a request for histopathologic examination of BCC. Similarly, pathologists write incomplete reports that lack important pathologic features. Having pre-set forms (electronic proforma) can help overcome missing information.

Vitamin D and ferritin correlation with chronic neck pain using standard statistics and a novel artificial neural network prediction model.

AIM: Despite the high prevalence of chronic neck pain, there is limited consensus about the primary etiology, risk factors, diagnostic criteria and therapeutic outcome. Here, we aimed to determine if Ferritin and Vitamin D are modifiable risk factors with chronic neck pain using slandered statistics and artificial intelligence neural network (ANN). METHODS: Fifty-four patients with chronic neck pain treated between February 2016 and August 2016 in King Abdullah University Hospital and 54 patients age matched controls undergoing outpatient or minor procedures were enrolled. Patients and control demographic parameters, height, weight and single measurement of serum vitamin D, Vitamin B12, ferritin, calcium, phosphorus, zinc were obtained. An ANN prediction model was developed. RESULTS: The statistical analysis reveals that patients with chronic neck pain have significantly lower serum Vitamin D and Ferritin (p-value <.05). 90% of patients with chronic neck pain were females. Multilayer Feed Forward Neural Network with Back Propagation(MFFNN) prediction model were developed and designed based on vitamin D and ferritin as input variables and CNP as output. The ANN model output results show that, 92 out of 108 samples were correctly classified with 85% classification accuracy. CONCLUSIONS: Although Iron and vitamin D deficiency cannot be isolated as the sole risk factors of chronic neck pain, they should be considered as two modifiable risk. The high prevalence of chronic neck pain, hypovitaminosis D and low ferritin amongst women is of concern. Bioinformatics predictions with artificial neural network can be of future benefit in classification and prediction models for chronic neck pain. We hope this initial work will encourage a future larger cohort study addressing vitamin D and iron correction as modifiable factors and the application of artificial intelligence models in clinical practice.

Subcutaneous accessory pain system (SAPS): A novel pain pathway for myofascial trigger points.

Despite the accumulating neuro-physiological evidence of myofascial pain, many clinicians are skeptical about its existence as a separate disease entity. No single theory can fully explain the four cardinal features of MPS; taut bands, local tenderness, local twitching and the characteristic pattern of referred pain. Bridging the gap between basic and clinical knowledge mandates coupling the local trigger point changes with the clinically seen distant somatically innervated referred pain. The main question addressed by the present theory is why do trigger points behave differently in comparison to the surrounding muscle tissue and are trigger points the primary problem or secondary to a primary pathology. We propose that trigger points have an extra-innervation system that connect them with other spinal structures such as the facet, the annulus and other trigger points with a role for the subcutaneous fascia as part of trigger points pathogenesis or passage for the extra-innervation. The extra-innervation system is Subcutaneous accessory pain system (SAPS). The novel SAPS system connecting trigger points to the spinal segments via dorsal rami is presented. Individuals with this accessory pathway are prone to myofascial pain, trigger point activation and segmental referred somatic pain similar to other axial spinal structures. Despite the high prevalence of myofascial pain, the mechanism is not universally agreed upon. Why do the trigger points act differently from surrounding muscle tissue and are almost constant in location in different individuals is controversial. Why does myofascial pain and its two components, trigger points and referred pain, exist or are more prevalent in some individuals than in others is unexplained. The correlation between axial spinal structures pathology and the trigger points is not explored well. The existing theories about trigger point formation and referred pain is scientifically credible for each separate component and the SAPS novel system can provide the link between the two.

Clinical Decision-Making in Chronic Spine Pain: Dilemma of Image-Based Diagnosis of Degenerative Spine and Generation Mechanisms for Nociceptive, Radicular, and Referred Pain.

BACKGROUND: Spine-related pain is a complex heterogeneous condition. Excessive reliance on radiological imaging might lead to overdiagnosis of incidental asymptomatic spinal changes and unnecessary surgery. Approaches to the clinical management of spine pain should (1) identify pain generators, types, patterns, and mechanisms; (2) confirm clinical suspension with a diagnostic injection; and (3) ensure that treatment is aimed at controlling pain and improving patient function rather than image-based surgical success. METHOD: This case series (7 cases) discusses commonly seen clinical presentation of spine pain analytically, with illustrations of possible pain generators, mechanisms, pathways, and pain types. Each case discusses pain types and location (axial nociceptive, referred, and radicular neuropathic), generators (degenerated disc, herniated disc, facet joint, and sacroiliac joint), pathways (sinuvertebral ventral ramus and medial and lateral branches dorsal ramus), and radiculopathy versus radicular pain, elaborating on coccydynia and cervicogenic headaches, epimere versus hypomere muscle embryology, function, innervation, and role in spine-related pain. RESULTS: Multiple pain generators might coexist in the same patient causing mixed pain types and referral patterns with multiple mechanisms and pathways. History review, physical examination, and diagnostic injections are the mainstays of diagnosis. CONCLUSIONS: Image-detected spondylosis might be an asymptomatic process. Clinical presentation is related to stenosis or pain. The mechanism of pain is related to compression, inflammation, or microinstability. Spine pain can be nociceptive axial, neuropathic radicular, and/or referred pain. Although image findings are helpful in radicular neuropathic pain from disc herniation, they are unreliable in nociceptive pain, and correlation with clinical and diagnostic injections is mandatory.

Adult primary cervical extra-osseous Ewing's sarcoma: A case report and short literature review.

INTRODUCTION: Primary spinal epidural extraskeletal Ewing's sarcoma (EES) is extremely rare, with a peak incidence in the second decade of life. EES in old people is challenging to treat due to the lack of specific guidelines. In this paper, I present a unique case of adult primary cervical epidural EES with a 13-month follow-up. A short literature review of the therapeutic approaches and prognosis is also presented. PRESENTATION OF CASE: I present a case of a 49-year old male patient who presented with right upper limb pain, numbness, hand grip weakness, and hyperreflexia of 3 months duration. Enhanced cervical magnetic resonance imaging showed a homogenously enhancing epidural and paravertebral soft tissue mass extending from the C6 to the T2 that appeared hypointense on T1 and hyperintense on T2. The patient underwent biopsy that confirmed EES via histopathology. Treatment with chemotherapy and radiotherapy resulted in tumor resolution and symptom relief. DISCUSSION: EES is a type of PNET. Surgical removal is generally the treatment of choice, followed by adjunctive chemotherapy and radiotherapy. In old patients with large tumors, a more conservative approach with biopsy, adjuvant chemotherapy and radiotherapy is recommended. CONCLUSIONS: Adult primary cervical epidural EES is a neurosurgical challenge due to the extension to the surrounding vital structures making the tumor not amenable for total resection as in the present case. In the absence of specific therapeutic guidelines, our case highlights the need to individualize the treatment modality according to age, tumor extension, and feasibility of total tumor resection.

Modification of Astrocyte Metabolism as an Approach to the Treatment of Epilepsy: Triheptanoin and Acetyl-L-Carnitine.

Epilepsy is a severe neurological disorder characterized by altered electrical activity in the brain. Important pathophysiological mechanisms include disturbed metabolism and homeostasis of major excitatory and inhibitory neurotransmitters, glutamate and GABA. Current drug treatments are largely aimed at decreasing neuronal excitability and thereby preventing the occurrence of seizures. However, many patients are refractory to treatment and side effects are frequent. Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults. In rodents, the pilocarpine-status epilepticus model reflects the pathology and chronic spontaneous seizures of TLE and the pentylenetetrazole kindling model exhibits chronic induced limbic seizures. Accumulating evidence from studies on TLE points to alterations in astrocytes and neurons as key metabolic changes. The present review describes interventions which alleviate these disturbances in astrocyte-neuronal interactions by supporting mitochondrial metabolism. The compounds discussed are the endogenous transport molecule acetyl-L-carnitine and the triglyceride of heptanoate, triheptanoin. Both provide acetyl moieties for oxidation in the tricarboxylic acid cycle whereas heptanoate is also provides propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis-the refilling of the tricarboxylic acid cycle.

Astrocyte-neuronal interactions in epileptogenesis.

Pentylenetetrazol, kainic acid, or pilocarpine can be used to induce seizures in animal models of epilepsy. The present Review describes disturbances in astrocyte-neuron interactions in the acute, latent, and chronic phases analyzed by magnetic resonance spectroscopy of brain tissue extracts from rats injected with [1-(13)C]glucose and [1,2-(13)C]acetate. The most consistent change after onset of seizures was the decrease in (13)C labeling of glutamate (GLU) from [1-(13) C]glucose regardless of brain area, severity, or duration of the period with seizures and toxin used. In most cases this decrease was accompanied by a reduction in glutamine (GLN) labeling from [1-(13)C]glucose, presumably as a direct consequence of the reduction in labeling of GLU and the GLU-GLN cycle. Amounts of GLN were never changed. Reduction in the content of N-acetyl aspartate (NAA) was first detectable some time after status epilepticus but before the occurrence of spontaneous seizures. This decrease can be an indication of neuronal death and/or mitochondrial impairment and might indicate beginning gliosis. It is known that gliosis occurs in the chronic phase of temporal lobe epilepsy in hippocampus, but astrocyte metabolism appears normal in this phase, indicating that the gliotic astrocytes have a somewhat reduced metabolism per volume. A decrease in (13)C labeling of GLU from [1-(13)C]glucose is a very sensitive measure for the onset of epileptogenesis, whereas reduction of NAA is first detectable later. In the chronic phases of the hippocampal formation, astrocyte metabolism is upregulated given that the number of neurons is reduced.

Percutaneous discectomy: minimally invasive method for treatment of recurrent lumbar disc herniation.

OBJECTIVES: Recurrent lumbar disc herniation has been reported in 5-11% of patients. Revision surgery carries a higher risk of complications due to epidural scar formation and difficulty in identifying the bony landmarks. The present study was conducted to apply an innovative procedure which optimally has lower complications, and decrease the need for major surgery for high risk patients. PATIENT AND METHOD: Our study presents six patients of recurrent herniation after past performed procedures such as microdiscectomy, or a laminectomy and discectomy who were readmitted and treated with APLD (automated percutaneous lumbar discectomy) as the first line. The APLD criteria for patient selection in the present study are those with predominantly leg pain that failed conservative treatment for at least 6 weeks and, after lumbar surgery for at least 6 months at the same level. RESULTS: Four of the patients have sciatica recovery signs ranging between excellent to good and, two showed no improvement. None of the screened patients in this study developed any serious complications. CONCLUSION: Although this is a small series with a short follow up duration, it can be postulated that in the absence of objective evidence of spinal instability, recurrent disc herniation with predominantly leg pain may be treated by APLD as a first line. This can be especially helpful in patients with high risk for anesthesia.

Isolated lipoma of filum terminale in adults: MRI findings and clinical correlation.

INTRODUCTION: Fat within the filum terminale is frequently seen on routine magnetic resonance imaging (MRI) of the lumbosacral spine (LSS), with prevalence of 1-5%. The objective of this study was to determine the prevalence and MRI features of isolated lipoma of filum terminale (LFT) in adult population and its correlation with the patient clinical presentations. METHODS: Prospective analysis of all lumbosacral MRI performed at King Abdullah University Hospital during a 21-month period. A total of 37 patients with LFT were included. Patients were divided into two groups. Group A patients have neurological deficit manifested by either motor, sensory or sphincter abnormality. Group B patients have normal neurological examination. Clinical findings were correlated with: A: thickness of LFT, B: length of LFT, C: distance of LFT from conus medullaris (CM), D: age of the patient. RESULTS: The prevalence of isolated LFT in our study was 3.2%. There was no significant correlation between the thickness or length of LFT and the presence of neurological deficit. The distance of LFT from CM was also not correlated with the patient clinical presentation. No significant difference in the age between the two groups. CONCLUSION: LFT in adult likely represent an incidental finding on routine lumbosacral MRI. Special attention for LFT in children is mandatory as it may indicate clinical tethering in otherwise normal appearing LSS.

[2,4-(13)C]ß-hydroxybutyrate metabolism in astrocytes and C6 glioblastoma cells.

This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4-(13)C]ß-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1-(13)C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry and media by (1)H magnetic resonance spectroscopy and HPLC. Using [2,4-(13)C]BHB and [1-(13)C]glucose it could be shown that C6 cells, in analogy to astrocytes, had efficient mitochondrial activity, evidenced by (13)C labeling of glutamate, glutamine and aspartate. However, in the presence of glucose, astrocytes were able to produce and release glutamine, whereas this was not accomplished by the C6 cells, suggesting lack of anaplerosis in the latter. We hypothesize that glioblastoma cells kill neurons by not supplying the necessary glutamine, and by releasing glutamate.

Primary spinal extradural hydatid cyst in a 4-year-old child.

The authors report a case of 4-year-old boy with primary spinal extradural hydatid cyst of the thoracic spine. The location is extremely rare. However, the case is unique because the patient is the youngest reported in the English language medical literature. Surgical excision is the gold standard therapy.

Conservative management of acute epidural hematoma in a pediatric age group.

OBJECTIVE: Craniotomy and evacuation is the standard treatment of acute epidural hematoma (EDH). Here, the authors report their experience in nonoperative management of acute EDH in children with mild head injury. METHODS: The authors retrospectively reviewed charts of patients with conservatively treated EDH at the Department of Neurosurgery, King Abdulla University Hospital, Irbid, Jordan, between August 2003 and October 2007. All patients had a Glasgow Coma Scale score of 14 or 15, and an initial computerized tomography (CT) scan demonstrating an EDH with or without skull fractures. Follow-up included neurological examination and brain CT. RESULTS: Six children (3 boys, 3 girls) with acute EDH were successfully managed at our department without surgical intervention. The Glasgow Outcome Scale score of all patients was 5, with no posttraumatic sequelae. Follow-up brain CT showed complete resolution of the EDH within 2-3 months. CONCLUSIONS: Our results demonstrated that pediatric EDH can be managed nonoperatively. The pronounced increase in the number of CT examinations for patients with head injuries has resulted in a greater proportion of EDH detected in conscious patients. We recommend such treatment be performed in specialized pediatric neurosurgical centers under close neurological observation.

Pentylenetetrazole affects metabolism of astrocytes in culture.

Cortical and cerebellar astrocytes were cultured in medium containing pentylenetetrazole (PTZ), a gamma-aminobutyric acid (GABA)(A) receptor antagonist, for 3 weeks (up to 6 mM) or 2 hr (10 mM). Cells were incubated in medium containing [U-(13)C]glutamate (0.5 mM) and unlabeled glucose (3 mM) for 2 hr and cell extracts and media were analyzed by (13)C magnetic resonance (MR) spectroscopy and high-performance liquid chromatography (HPLC). When cerebellar astrocytes were incubated with PTZ for 2 hr, the amount of glucose removed from the medium and glucose and [U-(13)C]glutamate oxidation were decreased. Metabolism in cortical astrocytes was affected only slightly; amounts of glutathione and aspartate were decreased. When cerebellar and cortical cells were cultured in the presence of PTZ for 3 weeks, the amount of glucose removed from the medium and lactate formed were increased, indicating increased glycolytic activity. Despite the increased intracellular [U-(13)C]glutamate concentration in both types of astrocytes cultured with PTZ, labeled glutamine and glutathione were unchanged, indicating intracellular compartmentation. The amount of cellular protein was decreased at 6 mM PTZ for cerebellar astrocytes and 1 mM for cortical astrocytes, indicating a differential sensitivity to the effects of PTZ. In conclusion, mitochondrial metabolism and glycolysis were decreased by short-term incubation with PTZ in cerebellar astrocytes, whereas long-term incubation affected both types of astrocytes, leading to increased glycolysis.

Changes of glial-neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole.

Pentylenetetrazole (PTZ) injection causes seizures in rodents and this is used in several models of epilepsy. In the present study a low dose (20 mg/kg) was injected into rats in order to analyze metabolic disturbances caused by subconvulsive amounts of PTZ. Intraperitoneal injection of PTZ was followed, 30 min later, by injection of [1-(13C)]glucose plus [1,2-(13C)]acetate and 15 min thereafter decapitation. Analyses of extracts from cerebrum, subcortex and cerebellum were performed using 13C NMRS and HPLC. Whereas convulsive doses of PTZ lead to most pronounced changes in cerebellum [J. Neurochem. 85 (2003) 1200], it could be shown that subconvulsive doses affected mainly amino acid metabolism in cerebrum. In glutamatergic neurons in the cerebrum PTZ affected both the metabolic and releasable pools of glutamate, whereas, in the subcortex and cerebellum only the metabolic pool was affected. This could be deducted from the findings that less [4-(13C)]glutamine, [3,4-(13C)]glutamate and [2-(13C)]aspartate, which are labeled from [1-(13C)]glucose, were detected in this area. Glial metabolism was also changed as evidenced by the decreased pyruvate carboxylation versus pyruvate dehydrogenation ratio both in cerebrum and subcortex. Comparison between convulsive and nonconvulsive doses of PTZ lead to the hypothesis that changes observed in the cerebellum are mainly due to seizures, whereas those in cerebrum and subcortex are coupled to the action of the chemical stimulant.

Pentylenetetrazole decreases metabolic glutamate turnover in rat brain.

Seizures were induced in rats by intraperitoneal injection of pentylenetetrazole (PTZ, 70 mg/kg), followed, 30 min later, by injection of [1-13C]glucose and [1,2-13C]acetate. Analyses of extracts from cortex, subcortex and cerebellum were performed using 13C magnetic resonance spectroscopy and HPLC. It could be shown that PTZ affected different brain regions differently. The total amounts of glutamate, glutamine, GABA, aspartate and taurine were decreased in the cerebellum and unchanged in the other brain regions. GABAergic neurones in the cortex and subcortex were not affected, whereas those in the cerebellum showed a pronounced decrease of GABA synthesis. However, glutamatergic neurones in all brain regions showed a decrease in glutamate labelling and in addition a decreased turnover in cerebellum. It could be shown that this decrease was in the metabolic pool of glutamate whereas release of glutamate was unaffected since glutamine labelling from glutamate was unchanged. Aspartate turnover was also decreased in all brain regions. Changes in astrocyte metabolism were not detected, indicating that PTZ had no effect on astrocyte metabolism in the early postictal stage.

Glial-neuronal interactions following kainate injection in rats.

Limbic seizures were induced in rats by intraperitoneal injection of the glutamate receptor agonist kainic acid, followed, 24h later by injection of [1-13C]glucose and [1,2-13C]acetate. Analyses of forebrain extracts were performed using 13C magnetic resonance spectroscopy and HPLC. A significant increase in label derived from [1,2-13C]acetate was observed in glutamine and glutamate. Label in most metabolites derived from [1-13C]glucose was unchanged, however, a decrease was observed in [2-13C]GABA, possibly due to reduced GABA release, 24h after kainic acid injection. It should be noted that only astrocytes are able to utilize acetate as a substrate efficiently, whereas acetyl CoA derived from glucose is metabolized predominantly in the neuronal tricarboxylic acid cycle. No significant differences were found in total amounts of amino acids between the two groups. Thus, these results indicate that turnover of metabolites was increased predominantly in astrocytes whereas glutamatergic neurons were not affected. Previous results obtained using the same model [Neurosci. Lett. 279 (2000) 169] showed an increased turnover in both glutamatergic and GABAergic neurons 2 weeks after kainic acid injection. Combining the results from the two studies, it can be suggested that increased astrocytic activity 1 day after epileptic seizures results, subsequently, in an increased amino acid turnover in neurons.

Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.