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Biomedical subjects

B Abou-Khalil

Publications and source records attributed to B Abou-Khalil.

At least 19 recordsLinked to original sources

An open-label study of levetiracetam at individualised doses between 1000 and 3000 mg day(-1) in adult patients with refractory epilepsy.

BACKGROUND: The novel antiepileptic drug (AED) levetiracetam (LEV, Keppra) is indicated as adjunctive therapy for partial epilepsy. The primary aim of this study was to measure the safety and tolerability of LEV individualised dosing in a heterogeneous refractory epilepsy population. METHODS: LEV was evaluated in a 10- to 16-week open-label, multicentre study in adult patients with epilepsy refractory to previous treatment with at least two AEDs. Individualised LEV doses up to 3000 mg x day(-1) were determined in an initial up-titration phase, and optimal doses were administered as adjunctive treatment during an 8- to 10-week evaluation period. Concomitant AEDs and their doses could not be changed during the study. Safety and tolerability were monitored by expression of adverse events as well as by retention rate. The effect of LEV on concomitant AED concentration was also studied. Efficacy was assessed using global clinical evaluation (GCE) scores, seizure frequency, and >or=50% responder rate. RESULTS: LEV therapy was initiated in 219 patients; 183 had localisation-related epilepsy and 37 had generalised epilepsy. In one patient, epileptic syndrome was defined as both localisation-related and generalised. About 81.7% (179/219) continued and completed treatment throughout the study, and 79% (172/219) chose to continue LEV in a follow-up study. The most common adverse events were asthenia, dizziness, and somnolence. Most adverse events occurred during up-titration. LEV treatment did not alter the concentration of concomitant AEDs. LEV improved GCE scores in 79.5% (152/191) of patients. LEV reduced the median total seizure frequency of all patients from a median of 2.25 seizures per week at baseline (n=219) to 1.10 seizures per week during the evaluation period (n=191 patients with at least one seizure count during evaluation). The >or=50% responder rate was 48.2% for all seizure types, 49.4% for partial-onset, and 51.4% for generalised-onset seizures. Throughout the evaluation period (i.e. from the start of the evaluation period until completion or early discontinuation), 26/191 (13.6%) had a 100% reduction in total seizure frequency, while in a follow-up study, 10.5% (18/172) were seizure-free for at least 6 months and 6.4% (11/172) were seizure-free for at least 1 year. CONCLUSION: LEV was well tolerated, as evidenced by limited adverse event reporting and the high retention rate, and appeared effective in both generalised and partial epilepsy.

Adolescent↗

Intraventricular monitoring for temporal lobe epilepsy: report on technique and initial results in eight patients.

OBJECTIVE AND IMPORTANCE: Resective surgery is an effective treatment for refractory temporal lobe epilepsy. In difficult cases, invasive monitoring may be needed to precisely lateralise and localise seizure foci of mesial temporal origin. The authors present a modified technique for image guided, endoscopic placement of an intraventricular electrode array (IVE) that abuts the amygdalo-hippocampal complex. METHODS: Eight patients with suspected mesial temporal lobe epilepsy had placement of an IVE in conjunction with other invasive electrodes. Seven of these patients also had subdural grid or strip electrodes and four had foramen ovale electrodes. Frameless image guidance was used to place a custom 10-contact depth electrode through a rigid neuroendoscope within the atrium of the lateral ventricle. Once proper orientation towards the temporal horn was confirmed, the IVE array was advanced into the temporal horn to the temporal tip. The endoscope was removed and electrode placement was confirmed through an intraoperative lateral skull radiograph and on visual inspection at the time of resection in two cases. RESULTS: The IVE was crucial for localisation in one patient and helped localisation in four others. Surgery was offered to seven patients. The only serious complication of IVE placement was a thalamic contusion presumably from an errant electrode tip. One electrode was inadvertently placed into the frontal horn. There were no deaths and no permanent morbidity associated with the procedure. CONCLUSION: Endoscopically placed temporal horn, intraventricular electrodes provide an alternative to transcortical depth electrode placement. The technique hopefully can avoid complications associated with multiple depth electrode placements, especially when bilateral amygdalo-hippocampal electrical recordings are desired, although there may be a steep learning curve.

Adolescent↗

Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation.

BACKGROUND: Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant syndrome characterized by febrile seizures (FS) and a variety of afebrile generalized seizure types. GEFS+ has previously been linked to mutations in two genes encoding the voltage-gated sodium channel alpha-subunit (SCN1A) and beta1-subunit (SCN1B). We studied a large family with FS and partial as well as generalized seizure types. METHODS: All but two living affected family members were interviewed and examined. Information on deceased affected family members was sought. EEG for 11 affected family members and one unaffected family member were obtained. Genetic linkage analysis and mutation screening of SCN1A were performed on blood samples from 16 affected individuals and their first-degree relatives. RESULTS: There were 27 affected family members; 18 were alive at the time of the study. All affected family members had FS; seven had FS only, and 19 also had afebrile seizures. Eleven individuals continued to have FS beyond 6 years of age. FS were complex in 12 family members, usually with prolonged duration. The index patient had right temporal lobe epilepsy and hippocampal sclerosis. Four other patients had strong historical evidence of temporal lobe epilepsy, and three others had nonlocalizing evidence of partial epilepsy. Pedigree analysis indicated autosomal dominant transmission. All affected individuals who were tested and one asymptomatic individual had a sodium channel mutation of SCN1A, an A-->C transversion at nucleotide 3809 resulting in the substitution of lysine 1270 by threonine in the D3/S2 segment (designated as K1270T). CONCLUSIONS: Our findings indicate that partial epilepsy preceded by FS can be associated with sodium channel mutations and may represent a variant of GEFS+.

Adolescent↗

Video-EEG in the diagnosis of paroxysmal events in children with mental retardation and in children with normal intelligence.

Video-EEG monitoring was performed to evaluate 193 children (91 females, 102 males; mean age 9.6 years, SD 5.7) who presented with paroxysmal events of uncertain etiology. Diagnosis of the type of event, i.e. epileptic or non-epileptic, was successfully established in 130 of 193 patients (67.3%). Seventy children (36%) had mental retardation* (MR). Children with MR were more likely (p<0.05) than children without MR to have events during the studies. Children with and without MR had strikingly similar frequencies of epileptic and non-epileptic events. In participants who had events recorded and characterized, epileptic seizures were identified in 67 children (51.5%), non-epileptic events in 54 children (41.5%), and both epileptic and non-epileptic events in nine children (7%). Improved diagnosis prompted appropriate management. This should encourage more frequent use of video-EEG in children, especially in those with MR, to differentiate epilepsy from behavioral disturbances so that specific treatment can be provided.

Adolescent↗

Orbito-frontal epilepsy masquerading as temporal lobe epilepsy-a case report.

Temporal lobectomy fails to control seizures in a considerable percentage of patients who do not have hippocampal sclerosis. One theoretical reason for failure of surgery is that some of these patients may in fact have extratemporal epilepsy. We present a 28-year-old woman with clinical and scalp electroencephalogram (EEG) evidence of right temporal lobe epilepsy (TLE) supported by functional imaging with interictal positron emission tomography (PET) and ictal single-photon emission computerized tomography (SPECT). An invasive EEG monitoring was prompted by the discovery of a small right orbito-frontal lesion on MRI. Monitoring documented seizure onset at the lesion, with rapid right temporal involvement. The patient was almost seizure-free after a lesionectomy. The index of suspicion of orbito-frontal epilepsy should be high in patients with apparent TLE when the scalp EEG and neuroimaging data are not congruent, or if temporal lobe pathology cannot be identified on structural imaging.

Adult↗

Low-dose stereotactic radiosurgery is inadequate for medically intractable mesial temporal lobe epilepsy: a case report.

The successful surgical treatment of medically refractory epilepsy is based on one of three different principles: (1) elimination of the epileptic focus, (2) interruption of the pathways of neural propagation, and (3) increasing the seizure threshold through cerebral lesions or electrical stimulation. Temporal lobe epilepsy, being the most common focal epilepsy, may ultimately require temporal lobectomy. This is a case report of a 36-year-old male with drug-resistant right mesial temporal lobe epilepsy who failed to obtain seizure control after stereotactic radiosurgery to the seizure focus. Complex-partial seizures occurred 6-7 times monthly, and consisted of a loss of awareness followed by involuntary movements of the right arm. EEG/CC TV monitoring indicated a right mesial temporal lobe focus, which was corroborated by decreased uptake in the right temporal lobe by FDG-PET and by MRI findings of right hippocampal sclerosis. Stereotactic radiosurgery was performed with a 4MV linac, utilizing three isocenters with collimator sizes of 10, 10, and 7 mm respectively. A dose of 1500 cGy (max dose 2535 cGy) was delivered in a single fraction to the patient's right amygdala and hippocampus. There were no acute complications. Following radiosurgery the patient's seizures were improved in both frequency and intensity for approximately 3 months. Antiepileptic medications were continued. Thereafter, seizures increased in both frequency and intensity, occurring 10-20 times monthly. At 1 year post radiosurgery, standard right temporal lobectomy including amygdalohippocampectomy was performed with subsequent resolution of complex-partial seizures. Histopathology of the resected temporal lobe revealed hippocampal cell loss and fibrillary astrocytosis, consistent with hippocampal sclerosis. No radiation-induced histopathologic changes were seen. We conclude that low-dose radiosurgery doses temporarily changed the intensity and character of seizure activity, but actually increased seizure activity long-term. If radiosurgery is to be an effective alternative to temporal lobectomy for medically intractable temporal lobe epilepsy, higher radiosurgery doses will be required. The toxicity and efficacy of higher-dose radiosurgery is currently under investigation.

Adult↗

Hashimoto's encephalopathy: documentation of mesial temporal seizure origin by ictal EEG.

Hashimoto's encephalopathy is a chronic relapsing and remitting encephalopathy associated with antithyroid antibodies. Seizures are a frequent manifestation, but are not well characterized in the literature with respect to their onset. We describe a 48-year-old patient with recurrent encephalopathy and seizures, and elevated antithyroid antibodies. One seizure was documented with video-EEG monitoring using scalp and sphenoidal electrodes. The ictal discharge originated in the left mesial-basal temporal region. MRI showed an increased T2 signal in the white matter of the centrum semiovale, but no temporal pathology. Symptoms resolved after treatment with prednisone and azathioprine. Hashimoto's encephalopathy should be considered in patients with unexplained encephalopathy and seizures, including those originating in the temporal lobe.

Arthritis, Rheumatoid↗

Adult myoclonic epilepsy: a distinct syndrome of idiopathic generalized epilepsy.

The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.

Adult↗

Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of 500 mg bid and 1500 mg bid levetiracetam as adjunctive therapy for refractory partial seizures in a double-blind, randomized, placebo-controlled, parallel-group, multicenter trial. METHODS: The authors studied patients with uncontrolled partial seizures (minimum 12 per 12 weeks), regardless of whether they became secondarily generalized, for 38 weeks. A 12-week baseline was followed by random assignment to adjunctive therapy with placebo (n = 95), levetiracetam 1000 mg/day (n = 98), or levetiracetam 3000 mg/day (n = 101). Upward titration over 4 weeks was followed by 14 weeks of fixed dose treatment, and concluded with an 8-week medication withdrawal period or entering a follow-up study. RESULTS: Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p </= 0.001 for both groups). More patients responded (defined as minimum 50% reduction in partial seizure frequency) to levetiracetam than placebo, with rates of 33. 0% in the 1000 mg/day and 39.8% in the 3000 mg/day group, compared to 10.8% in the placebo group (p < 0.001). Of 199 patients receiving levetiracetam, 11 became seizure free; no patient became seizure free in the placebo group. Treatment-emergent adverse events (>/=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence. CONCLUSION: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

Adolescent↗

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Adolescent↗

Statistically driven identification of focal metabolic abnormalities in temporal lobe epilepsy with corrections for tissue heterogeneity using 1H spectroscopic imaging.

1H spectroscopic imaging of N-acetyl-aspartate, creatine, and choline has proven to be a sensitive indicator for the lateralization of seizure foci in temporal lobe epilepsy. Previous studies have used right-left comparisons to identify the epileptogenic tissue assuming that alterations due to the disease process outweigh the effects of tissue heterogeneity. To evaluate the effectiveness of tissue heterogeneity corrected analyses, we evaluated three criteria for lateralization of the seizure focus: 1) a statistically driven method adjusted for tissue composition, 2) a single valued threshold, and 3) a single global index of the hippocampus. The statistically driven analysis lateralized all eight patients correctly, whereas the single threshold method incorrectly lateralized one case and the global index failed to identify a significant difference in two cases. These findings indicate that increased accuracy and sensitivity can be obtained by correcting for tissue heterogeneity when analyzing spectroscopy studies of temporal lobe epilepsy.

Adult↗

Safety of long-term treatment with tiagabine.

The aim of this study was to evaluate the safety of long-term treatment with tiagabine. We reviewed the case report forms of patients with refractory partial epilepsy who took tiagabine for longer than 6 months in two long-term studies. We classified all adverse events based on severity and persistence, and recorded the dose at onset of each adverse event. We then divided patients into those treated for 6-12 months, 12-24 months and > 24 months. We compared the adverse event profile and change in seizure frequency among the three groups. Forty-two patients took tiagabine for longer than 6 months. The mean duration of treatment was 22.6 months. The mean monthly seizure frequency was 12.7 at baseline and 8.1 at study termination (36% decrease). The most common adverse events were: tiredness (56%), headache (46%), dizziness (44%), visual symptoms (blurring, difficulty focusing, diplopia) (39%), altered mentation (32%), and tremor (31%). The adverse event profile was comparable among the three groups. Seizure frequency was significantly more improved in the > 24 months group. Long-term treatment with tiagabine is well tolerated. The most important predictor of long-term therapy with tiagabine was the degree of seizure improvement.

Adolescent↗

Absence seizures with evolution into generalized tonic-clonic activity: clinical and EEG features.

PURPOSE: To report the clinical and electrographic features of absence seizures evolving into generalized tonic-clonic (GTC) activity in six patients with idiopathic generalized epilepsy. METHODS: All patients were referred for evaluation of refractory seizures and underwent video-EEG monitoring after discontinuation of their antiepileptic drugs (AEDs). We analyzed the video-EEG recordings for seizure semiology as well as ictal and interictal activity. We also reviewed the initial clinical data in all patients. RESULTS: All patients were women, with a mean age of 27 years (range, 14-43 years). The mean age at seizure onset was 12 years (range, 5-15 years). Family history was positive for epilepsy in four patients. All patients had recorded seizures with an onset that was characteristic of generalized absence clinically and electrographically, with evolution into GTC activity. The EEG onset was with generalized 2.5-to 5-Hz spike-and-wave discharges, with evolution into faster rhythmic activity. Interictal EEG recordings showed generalized 2-to 5-Hz spike-and-wave discharges. All had normal background activity. All patients were treated with divalproex monotherapy. Five patients have been seizure free, and one had a single breakthrough GTC seizure during a follow-up period of 12-36 months. CONCLUSIONS: GTC activity may evolve from typical absence seizures. This seizure type should be included in the International Classification of Seizures. Its recognition and distinction from complex partial seizures with secondary generalization are important for appropriate therapy.

Adolescent↗

Topiramate in the long-term management of refractory epilepsy. Topiramate YOL Study Group.

PURPOSE: A total of 292 adult patients (mean age, 33 years) with partial and/or generalized seizures previously resistant to antiepileptic drug (AED) therapy (median baseline seizure rate, 12 seizures/month) were treated with open-label topiramate (TPM) in dosages of 100-1,600 mg/day. METHODS: The mean duration of TPM treatment was 413 days (range, 84-804 days), and the mean TPM dosage was 503 mg/day (range, 100-1,600 mg/day; median TPM dosage, 300 mg/day). Seizure reduction was calculated from seizure counts during the last 3 months and last 6 months of TPM therapy compared with baseline. RESULTS: Overall, >50% of patients achieved > or =50% seizure reduction. More important, 11% of patients were seizure-free for > or =3 months at the last visit; 10% of patients were seizure free for > or =6 months at the last visit. This robust therapeutic response was consistent for patients receiving TPM dosages >400 and <400 mg/day. The most commonly reported adverse events were related to the central nervous system. Over the 2.2-year treatment period, 19% of patients discontinued TPM therapy because of inadequate seizure control; 32% discontinued because of adverse events. Findings from this study show that TPM is a useful agent for long-term seizure control, with some patients becoming seizure free for extended periods despite failing previous AED therapy.

Adolescent↗

Brief antiepileptic drug withdrawal prolongs interval to next seizure.

OBJECTIVE: To evaluate the course of seizure control after reinstitution of antiepileptic drugs (AEDs) in patients whose AEDs were discontinued during inpatient EEG-video monitoring. METHODS: The authors studied prospectively patients with intractable epilepsy admitted for EEG-video monitoring with AED withdrawal. They examined seizure diaries in the 2 months preceding admission and recorded the number of seizures during hospitalization and for 2 months after discharge. They also recorded the interval between the last two seizures preceding admission (S-S pre), from the last seizure to admission (S-A), from discharge to the first seizure after discharge (D-S), and between the first and the second seizures following discharge (S-S post). RESULTS: Sixty patients qualified for the study. There was a significant decrease in seizure frequency in the 2 months after discharge compared with baseline (p = 0.02). For patients who had at least two seizures during follow-up, the mean D-S interval was significantly longer than mean S-S pre and S-S post (p < 0.005), whereas the latter two intervals were comparable. Prolongation of D-S was related to duration off AEDs and to the AED restarted, but not to the number or severity of seizures during monitoring. CONCLUSION: Seizure improvement after reinstitution of antiepileptic drugs (AEDs) is due primarily to prolongation of the interval from reinstitution of AEDs to the next seizure. This may reflect increased patient responsiveness to AED therapy after a drug "holiday" and has implications for experimental AED testing in the setting of presurgical evaluation.

Adolescent↗

Visual field defects after temporal lobe resection: a prospective quantitative analysis.

OBJECTIVE: To evaluate and quantify prospectively visual field changes in patients undergoing temporal lobe resections for intractable epilepsy. BACKGROUND: Visual field abnormalities occur after temporal lobe resections for epilepsy; however, we have not encountered published reports using automated static visual field analysis. METHODS: Humphrey visual fields (program 30-2) were obtained before and after partial temporal lobe resection in 32 consecutive patients with intractable epilepsy. A quantitative point-by-point analysis was made in the affected superior quadrant, and the defects were averaged for the whole patient group. RESULTS: Thirty-one patients developed a visual field defect, but none was aware of the defect. The points nearest fixation were relatively spared. The defects were greatest in the sector closest to the vertical meridian in the eye ipsilateral to the resection. The ipsilateral and contralateral mean field defects also differed in both topography and depth. A significant correlation was found between the extent of lateral temporal lobe resection and the degree of the defect in the contralateral eye. CONCLUSIONS: There are differences in the shape and depth of the ipsilateral and the contralateral field defects not previously reported. These findings demonstrate that certain fibers from the ipsilateral eye travel more anteriorly and laterally in Meyer's loop, and support the hypothesis that visual field defects due to anterior retrogeniculate lesions are relatively incongruous because of anatomic differences in the afferent pathways. Automated perimetry is a sensitive method of evaluating and quantifying visual field defects.

Adolescent↗

Generalized absence seizures with 10-15 Hz fast discharges.

OBJECTIVE: To report clinical and EEG features in 5 adults with unusual, fast rhythmic discharges accompanying absence seizures. DESIGN AND METHODS: The 5 patients presented with uncontrolled seizures. All had EEG-video monitoring with recorded seizures. Video seizures were reviewed and ictal as well as interictal epileptiform activity was analyzed. The patients were followed up after appropriate therapy for a minimum of 6 months. RESULTS: There were 3 women and two men, with a mean age of 37 years (range: 23-59). Two patients had onset of absence seizures in childhood, one in adolescence and two after age 20. All patients also had generalized tonic-clonic seizures. Ictal EEG recordings showed generalized spike and wave (SW) discharges of variable dominant frequencies (2.5-6 Hz) and intermingled 10-15 Hz generalized rhythmic discharges which also occurred in isolation or as the dominant activity. Interictal recordings showed similar but shorter 2.5-6 Hz generalized SW discharges. The background activity was normal in 3 patients and mildly slow in two who had very frequent absence seizures during the recording period. Four patients became seizure free and one had 75% improvement on appropriate antiabsence therapy. CONCLUSIONS: The fast 10-15 Hz rhythmic discharges that we report appear to occur mostly in adult patients with absence, as well as, generalized tonic-clonic seizures. They can occur in isolation or be embedded in more typical SW discharges accompanying typical absence seizures. Their presence does not imply a poor prognosis for seizure control.

Adult↗

The value of combined ambulatory cassette-EEG and video monitoring in the differential diagnosis of intractable seizures.

OBJECTIVE: To evaluate the ability of combined ambulatory cassette-EEG and video monitoring (ACV) to establish a diagnosis in patients with attacks of unknown nature and its impact on their treatment. METHODS: We evaluated ACV in 125 consecutive patients with attacks of unknown nature. Most had intractable attacks suspected of being non-epileptic. Antiepileptic drugs (AEDs) were discontinued or reduced at the start of the procedure. The median duration of monitoring was 3 days (range 1-10). The ACV results and patient records were reviewed, and patients were called for additional follow-up when feasible. RESULTS: Attacks were recorded in 101 patients. They were epileptic in 20 patients, psychogenic in 60, both in 3, and of unknown nature in 18 (usually subjective episodes). The study resulted in AED discontinuation at discharge in 46 patients with recorded psychogenic seizures and 6 with recorded attacks of unknown nature. Three-quarters of patients followed up were free of attacks or improved. CONCLUSIONS: ACV was effective in providing a diagnosis in two-thirds of patients. If psychogenic seizures are suspected in patients on AEDs, ACV may provide the diagnosis and may help exclude epilepsy, without the need for standard EEG-CCTV, which can then be reserved for patients undergoing presurgical evaluation.

Adolescent↗