Aim: Intramedullary spinal cord tumors (IMSCT) are rare neoplasms of central nervous system but require proper evaluation and management to ensure a good outcome. This study was carried out to evaluate the functional outcome of IMSCT following surgery and to decipher the factors affecting optimal outcome of these cases. Materials and Methods: A prospective clinical study was carried out at a tertiary care center from 2003 to 2012. Forty three patients with intramedullary tumors diagnosed on magnetic resonance imaging were included. Their clinical details, neurological findings and demographic data were recorded. The patients were then subjected to surgery and adjuvant radiotherapy. The patients were followedup clinically and radiologically, and all parameters examined and recorded. Results: Sensory and motor impairment was present preoperatively in majority of patients (n = 39 and n = 38, 90.7% and 88.4%, respectively). Gross total excision was performed in 30 cases (69.76%). The most common histological diagnosis was ependymoma (n = 21, 48.8%). Postoperatively 32 patients (74.4%) were in McCormick functional Grade I or II improving from 13 cases (30.2%) in Grade I or II preoperatively. Fifteen of 17 patients in Medical Research Council (MRC) Grade III and 10 out of 12 patients in Grade MRC IV improved. No mortality was recorded during the entire period of follow-up (mean: 22, range: 3-96 months). Eight patients (18.6%) had recurrence till the last follow-up visit. Conclusions: Preoperative neurological grade was the most important predictor of functional outcome. Gross tumor excision was the best surgical modality to improve event free survival. High-grade tumors had higher rates of recurrence but no effect on functional outcome.

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Acute subdural hematomas (ASDHs) are rarely reported in the literature. In general, it is due to head trauma, but if the traumatic event is very mild, it is inadequate to explain the ASDH occurrence. Risk factors for the development of spontaneous ASDH include hypertension, vascular abnormalities and deficit of coagulation. We present two cases of ASDH in patients with the coagulation deficit and review of the literature to understand the coagulation factors role and platelet role in the management of ASDHs.

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Objective: Ossification of the posterior longitudinal ligament (OPLL) is a complex multi-factorial disease process having both metabolic and biomechanical factors. The role of surgical intervention as well as the choice of approach weather anterior or posterior is ambiguous. The objective of this study was to assess the surgical out come and post operative functional improvement in patients with cervical OPLL at a tertiary care centre. Patients and Methods: This prospective study included 63 patients of cervical OPLL who underwent either anterior and/or posterior surgeries in Department of Neurosurgery, Nizam's Institute of Medical Sciences, Hyderabad between June 2009 to May 2011. Patient's data including age, sex, pre and post operative functional status, radiographic findings and OPLL subtypes were recorded and analyzed over a follow up ranging up to minimum two years. Results: The mean age of the patients was 51.1 (range 30-80 years) involving 14 women and 49 men. Out of 63 patients, 14 patients underwent surgery by anterior approach (corpectomy and fusion) and all of them improved (P = 0.52). 49 patients underwent surgery by posterior approach where decompressive laminectomy was performed in 40, laminectomy with instrumentation was done in 5, laminoplasty was done in 3 and 1 patient underwent both anterior and posterior surgeries. Of those who underwent posterior surgery, 40 patients improved, 7 remained the same as their preoperative status (who were having signal intensity changes on T2W MRI) and 2 patients deteriorated in the immediate post operative period and then showed gradual improvement. All the patients were followed up for 24 months. The mean pre-operative Nurick grade was 2.82 which later on improved to 2.03 post surgery (P < 0.05). Minor complications included wound infections in two patients (1.26%). Conclusions: Anterior cervical decompression and reconstruction is a safe and appropriate treatment for cervical spondylitic myelopathy in the setting of single or two level OPLL. Laminectomy or laminoplasty is indicated in patients with preserved cervical lordosis having three or more levels of involvement. Younger patients with good pre operative functional status and less than 2 levels of involvement have better outcome following anterior surgery.

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Introduction: Traumatic brain injury (TBI) is a major cause of disability. Depression is one of the major squeal of TBI in both in-patient and out-patient populations. Depression is associated with numerous negative outcomes, thus affecting quality-of-life (QOL) adversely in these patients. Addressing depression in treatment regimen of TBI may improve QOL of these patients. Objective: The present study is designed to evaluate the role of sertraline in post TBI depression and its impact on QOL. Materials and Methods: Eighty male patients with post TBI depression were included in the study among the 250 male patients of mild to moderate TBI recruited for the evaluation. Half of the patients were given sertraline 50 mg PO, whereas other half served as control without sertraline treatment. Participants were assessed on Glasgow Coma scale, Patient Health Questionnaire-9 (PHQ-9) and World Health Organization QOL (WHOQOL) at regular interval till the end of 6 months. Result: Depression was found in 35.6% of total patients recruited. Most of the patients (63.1%) were below 35 years of age. Depression was more common in mild TBI cases than those with moderate TBI (53.7% vs. 46.25%, P = 0.04). Left side brain injury (56.25%) with cerebral contusions was more commonly associated with depression (P = 0.04). Patients in sertraline group responded well to treatment with significant improvement in mod symptoms (PHQ-9 score 14.88 ± 3.603 vs. 5.33 ± 2.98, P = 0.04)). All the four domains of QOL improved significantly in sertraline group than the control group with sertraline treatment. Conclusion: Management of TBI should also focus on treatment of associated mood symptoms, which is likely to be associated with poor QOL in these patients. Sertraline has been found to be effective in the treatment of depression with significant improvement in QOL in TBI patients.

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We report two cases with giant intramedullary epidermoid cysts in the thoracolumbosacral and lumbosacral regions with varied presentations. Magnetic resonance (MR) imaging of the thoraco lumbar spine in case 1revealed an intramedullary elongated mass extending from T10 to S2 level causing significant widening of the spinal canal while MR imaging of lumbosacral spine in case 2 showed straightening of the lumbar spine and spina bifida at L5 level with conus at L3 and a lobulated long segment intramedullary solid cystic lesion extending from L2 to S2 veterbrae. The lesion was surgically resected and the pathology revealed an epidermoid cyst. Epidermoid cysts of the spinal cord are rare tumours in the adult population which may be congenital or acquired. Symptoms arising from epidermoid cysts vary with the level of involvement. The treatment of epidermoid cysts is surgical and if possible, complete removal is the goal.

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Arnold-Chiari malformations (ACM) of the brain result from aberrations in the development of the posterior fossa resulting in its smaller volume leading to tonsillar herniation. The most common type includes Type I ACM where tonsillar descent reaches up to either C1 or C2 along with cervico-dorsal syringomyelia. The surgery (foramen magnum decompression, [FMD]) is usually straight forward and includes sub-occipital craniectomy and cervical laminectomy based on the level of descent. Rarely inadequate cervical laminectomy of C1 arch may result in residual compression at the level of obex even after "lax" duraplasty. A cervico-dural angle (angle between the neo-dura and cervical dura) at level foramen magnum can be observed in these patients. This angle is usually obtuse in imaging of cranio-vertebral junction (CVJ) of normal people and in postoperative patients of Chiari malformations where normal anatomy is restored. Inadequate C1 laminectomy may result in an acute cervico-dural angle with residual compression at the level of CVJ. Therefore, C1 laminectomy becomes a key step in FMD surgery that is often underemphasized, and neurosurgeons should be careful in doing it adequately.

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Objective: The objective of this prospective cohort study was to analyse the characteristics of severe Traumatic Brain Injury (TBI) in a regional trauma centre Hospital Kuala Lumpur (HKL) along with its impact of various prognostic factors post Decompressive Craniectomy (DC). Materials and Methods: Duration of the study was of 13 months in HKL. 110 consecutive patients undergoing DC and remained in our centre were recruited. They were then analysed categorically with standard analytical software. Results: Age group have highest range between 12-30 category with male preponderance. Common mechanism of injury was motor vehicle accident involving motorcyclist. Univariate analysis showed statistically significant in referral area (P = 0.006). In clinical evaluation statistically significant was the motor score (P = 0.040), pupillary state (P = 0.010), blood pressure stability (P = 0.013) and evidence of Diabetes Insipidus (P < 0.001). In biochemical status the significant statistics included evidence of coagulopathy (P < 0.001), evidence of acidosis (P = 0.003) and evidence of hypoxia (P = 0.030). In Radiological sector, significant univariate analysis proved in location of the subdural clot (P < 0.010), location of the contusion (P = 0.045), site of existence of both type of clots (P = 0.031) and the evidence of edema (P = 0.041). The timing of injury was noted to be significant as well (P = 0.061). In the post operative care was, there were significance in the overall stability in intensive care (P < 0.001), the stability of blood pressure, cerebral perfusion pressure, pulse rates and oxygen saturation (all P < 0.001)seen individually, post operative ICP monitoring in the immediate (P = 0.002), within 24 hours (P < 0.001) and within 24-48 hours (P < 0.001) period,along with post operative pupillary size (P < 0.001) and motor score (P < 0.001). Post operatively,radiologically significant statistics included evidence of midline shift post operatively in the CT scan (P < 0.001). Multivariate logistic regression with stepwise likelihood ratio (LR) method concluded that hypoxia post operatively (P = 0.152), the unmaintained Cerebral Perfusion Pressure (CPP) (P = 0.007) and unstable blood pressure (BP) (P = <0.001). Poor outcome noted 10.2 times higher in post operative hypoxia [OR10.184; 95% CI: 0.424, 244.495]. Odds of having poor outcome if CPP unmaintained was 13.8 times higher [OR: 13.754; CI: 2.050, 92.301]. Highest predictor of poor outcome was the unstable BP, 32 times higher [OR 31.600; CI: 4.530, 220440]. Conclusion: Our series represent both urban and rural population, noted to be the largest series in severe TBI in this region. Severe head injury accounts for significant proportion of neurosurgical admissions, resources with its impact on socio-economic concerns to a growing population like Malaysia. This study concludes that the predictors of outcome in severe TBI post DC were postoperative hypoxia, unmaintained cerebral perfusion pressure and unstable blood pressure as independent predictors of poor outcome. Key words: Decompressive craniectomy, prognostication of decompressive craniectomy, prognostication of severe head injury, prognostication of traumatic brain injury, severe head injury, severe traumatic brain injury, traumatic brain injury.

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Hematogenous bone metastases from endometrial carcinoma are not frequent and their treatment is a matter of debate. We describe an extremely rare case of calvarial metastasis from endometrial carcinoma in an 80-year-old woman treated by means of one-step surgical radical resection and heterologous cranioplasty, along with a review of the literature regarding epidemiology, clinico-radiological features, prognosis, and management of skull metastases.

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Background: With the advancement of technologies there is more interest in the maintenance of the spine's biomechanical properties focusing on the preservation of the functional motion segment. In present article we describe our experience with 25 cases managed with artificial cervical discs with 28 Solis cage following cervical discectomy with a mean follow-up period of 7.5 year. Materials and Methods: All surgeries were performed by single surgeon from March 2004 to June 2005 with a follow-up till date. Patients with symptomatic single or multiple level diseases that had no prior cervical surgery were candidates for the study. Cohort demographics were comparable. Standardized clinical outcome measures and radiographic examinations were used at prescribed post-operative intervals to compare the treatment groups. Relief in radicular pain, cervical spine motion, and degenerative changes at follow-up were noted. Results: In a total 53 cases, the mean age in prosthesis group was 47 years (age range: 30-63 years) and mean age in cage group was 44 years (32-62 years). Mean hospital stay was 2.7 days in both the groups. At 4 weeks complete cervical movements could be achieved in 19 cases in artificial disc group. Maintenance of movement after 7.5 years was in 76% of these patients. Lordosis was maintained in all cases till date. There was no mortality or wound infection in our series. Conclusions: We conclude that artificial cervical disc could be an alternative to fixed spinal fusion as it represents the most physiological substitute of disc. However, there is need for further studies to support the use of artificial cervical disc prosthesis.

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The coexistence of a pituitary macroadenoma and a tuberculum sellae meningioma is very rare. This article demonstrates the surgical technique of the simultaneous resection of a pituitary macroadenoma and a tuberculum sellae meningioma using an endoscopic, endonasal, biportal, transsphenoidal approach. A 36-year-old woman presented with frontal headache and extended visual field loss of the right eye. She underwent cranial magnetic resonance imaging (MRI) revealing a 2 × 2× 2.5 mm contrast-enhancing intrasellar and suprasellar lesion with compression of the optic chiasma. The coexistence of a pituitary macroadenoma and meningioma was suggested. A biportal endoscopic endonasal transsphenoidal approach was performed to remove both lesions. The histological results confirmed the coexistence of the pituitary macroadenoma and meningioma, World Health Organization (WHO) grade I. The endoscopic, endonasal, transsphenoidal approach is a safe and reliable minimal invasive surgical alternative for resection of the intra-, supra- and parasellar lesions, avoiding additional craniotomy.

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Cerebral Nocardiosis is a rare, challenging, opportunistic infectious disease of the central nervous system occurring in both immunocompetent and immunocompromised hosts. It often results in intraparenchymal abscess formation, which represents only 2% of all cerebral abscesses. The diagnosis of cerebral Nocardiosis is seldom based on imaging. Bacteriological diagnosis is often reached only after surgical excision of the abscess. We report a rare case of brain abscess caused by Nocardia species in a 20-year-old immunocompromised lady. Total surgical excision of the abscess, prompt bacteriological diagnosis based on smear and culture of the pus and initiation of specific antimicrobial therapy (trimethoprim and sulfamethoxazole) resulted in good clinical outcome.

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Introduction: Colloid cysts are benign space-occupying lesions that account for 0.5-1.0% of brain tumors and arise from the velum interpositum or the choroid plexus of the third ventricle. Material and Methods: We are describing a modified surgical technique that combines the positive attributes of being minimalistic, while retaining the effectiveness of microsurgery. In all 20 consecutive symptomatic patients with a preoperative magnetic resonance imaging (MRI) diagnosis of colloid cyst who came to the senior author between 2008 and 2011 were included in the study. The patient was kept supine with the head positioned neutrally in the sagittal plane and neck flexed at 20°. The tube of a 5 ml plastic syringe having an external diameter of 13 mm and an internal diameter of 12.6 mm was cut toward the nozzle end to the appropriate length depending upon the cortical thickness measured on the preoperative MRI. Results: The average operative time was around 90 min with maximum of 120 min. None of the patients had seizures preoperatively or postoperatively and in all cases antiepileptic medication could be stopped after 3-6 month of surgery. Two patients had short-term memory impairment which returned to near normal by 1-year following surgery. Conclusion: A volume of 5 ml plastic syringe port technique decreases the operative morbidity and operative time. The wider corridor of working makes the simultaneously maneuverability of two surgical instruments feasible enhancing safety and completeness of excision.

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A 22-year-old man presented with a large, soft, compressible swelling in the right occipito-parietal region. Fine needle aspiration cytology revealed blood only. The lesion was excised and histopathology studies revealed it to be a diffuse neurofibroma.

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Traumatic bilateral basal ganglia bleed is extremely rare. It is defined as a hemorrhagic lesion located in the basal ganglia or neighboring structures such as the internal capsule and the thalamus. This report describes a 37-year-old man who had large bilateral basal ganglia hemorrhage (BGH) with subdural hematoma and traumatic subarachnoid hemorrhage. With regards to an etiology of bilateral hemorrhage of the basal ganglia, we could not disclose any possible cause except head injury in spite of full diagnostic work-up. Our final diagnosis was bilateral traumatic BGH (TBGH). The pathomechanism of such injuries is still not clear and it is proposed to be due to shear injury to the lenticulostriate and choroidal arteries. Rather than any features of the TBGH itself, duration of coma and/or associated temporal herniation predicted slower recovery and worse outcome. Bilateral TBGH is an extremely rare entity, compatible with a favorable recovery, if not associated with damage to other cortical and subcortical structures and occurring in isolation. TBGH can be considered as a marker of poor outcome rather than its cause. The BGHs seem to be hemorrhagic contusions resulting from a shearing injury, due to high velocity impact.

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Introduction: Surgical management of foramen magnum (FM) tumors is challenging by virtue of their location and vital neurovascular relationships. The ideal approach to anterior/anterolateral tumors continue to evoke controversy even in the modern era. In this article, we present and discuss our experience in the surgical management of these tumors. Materials and Methods: This retrospective study includes 29 consecutive patients (mean age 36.6 years, M: F = 2.63:1) of extramedullary tumors at the surgical foramen magnum, operated at our center, between 2007 and 2012. Results: Their mean duration of symptoms was 14. 6 months. A majority of the patients presented with motor symptoms (quadri/paraparesis, n = 21, 72.4%), neck pain with/without suboccipital radiation (n = 16, 55.2%) and sensory symptoms like tingling/numbness (n = 16, 55.2%). There were nine extradural (31%) and 20 intradural tumors (69%). Most of the tumors were located posterolateral to the neuraxis (n = 13, 44.8%). Nerve sheath tumors (n = 11, 38%) and meningiomas (n = 5, 17.2%) were the most commonly encountered histologies in our series. The standard posterior approach was the most frequently employed surgical approach (n = 20, 69%). Operative mortality and morbidity were 3.4 and 18.9%, respectively. At a mean follow-up of 27.3 months, 13 out of the 18 available patients improved. Conclusion: A majority of the foramen magnum tumors are amenable to excision via the standard posterior approach. Small anterior dural-based meningiomas/recurrent tumors may require a lateral approach like the far lateral approach.

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Juvenile Xanthogranuloma (JXG) is a rare disorder of central nervous system. It rarely produces compressive myelopathy. On reviewing world literature, we could find only nine cases of this disease involving spine and of which only four cases were in adults' i.e., 18 years and above. We are presenting a case of Spinal JXG in an18-year-old male with thoracic compressive myelopathy presenting as short duration progressive paraparesis. Magnetic Resonance Imaging of Spine showed mass lesion in epidural space compressing cord from behind without any bony involvement at D7 to D10 vertebral segment. It was isointense on T1 and hyperintense on T2 with no contrast enhancement. D7 to D10 Laminectomy with complete excision of firm epidural mass was carried out. The histopathology with tumor markers confirmed the diagnosis of JXG. Post-operative neurological recovery in this patient was good. His power improved to grade 5/5 with decreased spasticity. Follow-up MRI at 3 months showed no residual tumor. This case appears to be the first in the series with entirely extradural component in adult thoracic spine.

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Introduction: Aneurysmal subarachnoid hemorrhage (SAH) is a devastating event with a high rate of morbidity and mortality. With the improvement of diagnostic modalities and the adoption of different screening strategies, more aneurysms are being diagnosed prior to rupture. Based on large multi-center trials, size has become the most important determinant of treatment decisions. Unfortunately, these studies did not take into account the regional and racial variations, challenging the generalizability of their results. Material and Methods: We conducted a retrospective analysis on a series of 192 patients harboring 213 aneurysms. Results: The critical finding in our study is that the majority of patients presenting with SAH due to ruptured aneurysms are <10 mm in size. Conclusion: Decision to treatment of a given unruptured intracranial aneurysm should be individually assessed and not taken from general international literature as this may mistakenly apply factors from one population to another.

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True Recurrent artery of Heubner (RAH) aneurysms are extremely rare and only three cases have been reported in the literature. We report a case of RAH aneurysm in a patient with World Federation of Neurosurgical Societies grade one subarachnoid hemorrhage (SAH), detected only on delayed cerebral angiography. We propose that an aneurysm in this location should be considered in the differential diagnosis of angiogram-negative SAH, and all vascular imaging studies be carefully scrutinized for RAH aneurysm

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Brainstem cavernomas (BC) comprise about 5-18% of intracranial vascular malformations. The annual hemorrhage rate varies depending on the study design ranging from as low as 0.25% per patient-year in a retrospective study ^[2] to 1.6-3.1% per patient-year in prospective studies. ^[4],[5] The annual event rate is significantly higher in deep (brainstem, diencephalon) and infratentorial cavernomas when compared to their counterparts in other locations. ^[5] The management of BC can be conservative or surgical depending upon the mode of clinical presentation. Surgical excision of a BC is a challenge because of critical anatomy. We present a case of BC, which was totally excised with anterior petrosal approach. Anterior petrosal approach has been used for excision of BC in only 17 cases until now. ^[6] The use of preoperative diffusion tensor imaging, tractography, intra-operative navigation, and cranial nerve monitoring will help in reducing the morbidity.

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Marjolin's ulcer invading the skull, dura mater, and the brain is quite exceptional. We report such a rare case of massive Marjolin's ulcer arising in the chronic scar tissue of the scalp of an elderly male. The ulcer had invaded the skull, dura mater, and underlying brain tissue. The patient was managed successfully by wide excision and scalp reconstruction. The importance of appropriate and timely wound management of scar ulcers with high malignant potential is highlighted. The role of multidisciplinary approach in the scalp reconstruction is discussed.

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Retro-bulbar hydatid cysts are extremely uncommon, while nonorbital forms are frequently encountered disease in underdeveloped countries. Most of these are situated in the superolateral and superomedial angle of the orbit. We report a case of recurrent primary hydatid cysts of the orbit, situated in different locations in the orbit. A 35-year-old female patient was admitted to Department of Neurosurgery with proptosis, ptosis and watering from left eye. She also complained for headache with excruciating pain in left eye and loss of vision in left eye. Neurological examination revealed limited ocular mobility in all directions. Visual acuity was reduced to finger counting at 2-feet distance. Papilledema was found in ophthalmic examination. This case was considered as recurrence of primary infection because there was no previous history of hydatid disease and no finding of liver and lung cysts on radiological examinations. Treatment of orbital hydatid cyst, early diagnosis, surgical excision and systemic use of albendazole are suggested.

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Choroid plexus papillomas (CPPs) are rare intracranial neoplasms, especially in the third ventricle. The most common site of presentation of these lesions is in the fourth ventricle in adults and lateral ventricles in children . We report a male child with a posterior third ventricular CPP who presented with the symptoms of increased intracranial pressure. Magnetic resonance imaging revealed hydrocephalus related to a mass in the posterior third ventricle, occluding the aqueduct of Sylvius. After endoscopic third ventriculostomy, tumor was approached through the infratentorial-supracerebellar approach and completely excised. Pathological examination revealed a typical CPP. This entity should be considered an extremely rare cause of a lesion in the posterior third ventricle.

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L'hermitte-Duclos disease (LDD) is an extremely rare cerebellar lesion of uncertain etiology. Occasionally, the patients with LDD may even have sudden neurological deterioration due to acute heniation as seen in the present case report. It is also imperative to distinguish this disease from other malignant lesion of the cerebellum and cerebellar malformations with its varied natural course of history and hence better ability to prognosticate such patients. Herein, we reported a successfully treated case of LDD following a long history of vaguely defined neurological complaints in an elderly patient and reviewed the literature.

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Lesions occupying the anterior cranial fossa may arise de novo or are extensions from the sino-nasal areas with a handful of differentials in either group. The imaging findings, though to a large extent standardized are not full proof. Primary central nervous system lymphoma and sino-nasal lymphoma are uncommon variants of extranodal non-Hodgkin's lymphoma (NHL). We encountered a 35-year-old lady presenting with headache and seizures with a mass lesion involving the ethmoids with invasion into the anterior cranial fossa diagnosed as T-cell extranodal NHL. Gross total resection and reconstruction of the skull base were done. She was treated with chemotherapy and radiotherapy and is doing well at 6 months follow-up. This is the first report of a sino-nasal T-cell lymphoma invading the brain-parenchyma in an immuno-competent person. Sino-nasal primary T-cell lymphoma presenting as skull base pathology should form an essential differential diagnosis along with other routine lesions of anterior cranial fossa. Since these lesions have a good response to chemo and radiotherapy, a trans-nasal biopsy may obviate the need of a craniotomy if neurosurgeons are aware of this rare entity.

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Pleomorphic xanthoastrocytoma (PXA) is a rare slow growing tumor which accounts for <1% of all astrocytic neoplasms. PXA usually affects young patients in their second decade of life and carries a favorable prognosis. We present the clinical, radiological and histopathological features of PXA involving the left temporal lobe in an 84-year-old male with right upper motor neuron facial paresis of 2 weeks duration. Histopathology confirmed the diagnosis of PXA. Our case is unique in that our patient is the oldest one reported in the literature with favorable histopathological features. The occurrence of these tumors in elderly patients may indicate an aggressive behavior with unfavorable outcome. Gross total resection achieves higher recurrence free and overall survival rates.

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Granulocytic sarcomas (GSs) or myeloid sarcoma or chloroma are rare, destructive, extramedullary tumor masses that consist of immature granulocytic cells. We present case of a 35-year-old man presenting as monoparesis, diagnosed to have cervical intradural extramedullary mass lesion with an extradural extension. Although the history or physical examination had no symptoms and signs suggestive of leukemia, bone marrow study and blood picture indicated chronic myeloid leukemia. Surgical decompression was done, and histopathological examination was consistent with GS. GSs have been observed in patients with acute myelogenous leukemia, chronic myelogenous leukemia, and other myeloproliferative disorders, but rarely have been reported as first presentation of the disease.

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