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Neuro-oncology KEY POINTS ¢ Meningioma is the most common primary type of central nervous system tumor; they typically have a smooth, rounded shape and often a “tail” that tracks along the dura outside the brain parenchyma and homogenous enhancement on postcontrast MRI. e Meningiomas are resected only if accompanied by sig- nificant clinical deficits, drug-resistant seizures, severe headaches, or peritumoral edema.

e Meningiomas are resected only if accompanied by sig- nificant clinical deficits, drug-resistant seizures, severe headaches, or peritumoral edema. Glioblastoma Multiforme Glioblastoma multiforme (Figure 33) is the most common and most aggressive glioma subtype in adults. Previous exposure to medical therapeutic radiation is the only consistent risk factor for developing gliomas. There is no evidence that environmen- FIGURE 32. Coronal postcontrastT1-weighted MRI showing a left parafalcine meningioma. The tumor enhances homogeneously with contrast, which makes it tal electromagnetic fields, cell phones, or smoking increase look like a “lightbulb.” Note the “dural tail” tracking the enhancement from the tumor risk. Gliomas rarely metastasize, and routine evaluation tumor to adjacent, thickened dura (arrow). of patients with glioblastoma multiforme with lumbar punc- ture or MRI of the spinal cord is not recommended unless rounded shape and often a “tail” that tracks along the dura dictated by focal findings. outside the brain parenchyma (Figure 32). On noncontrast An MRI typically shows a large, space-occupying lesion images, meningiomas may be hypointense or isointense and with central necrosis, mass effect, and surrounding edema. thus not readily seen. Because of their characteristic MRI Lower-grade gliomas may not enhance. Treatment is usually appearance, many meningiomas are followed clinically, with- resection, if possible, followed by radiation and chemotherapy. out resection or biopsy, unless they are accompanied by Temozolomide, nitrosoureas, and bevacizumab can be used. significant clinical deficits, drug-resistant seizures, severe Prognosis is dependent on pathologic type; 5-year survival headaches, or peritumoral edema. rates for glioblastoma multiforme are less than 10%, and

Glioblastoma Multiforme Glioblastoma multiforme (Figure 33) is the most common and most aggressive glioma subtype in adults. Previous exposure to medical therapeutic radiation is the only consistent risk factor for developing gliomas. There is no evidence that environmen- FIGURE 32. Coronal postcontrastT1-weighted MRI showing a left parafalcine meningioma. The tumor enhances homogeneously with contrast, which makes it tal electromagnetic fields, cell phones, or smoking increase look like a “lightbulb.” Note the “dural tail” tracking the enhancement from the tumor risk. Gliomas rarely metastasize, and routine evaluation tumor to adjacent, thickened dura (arrow). of patients with glioblastoma multiforme with lumbar punc- ture or MRI of the spinal cord is not recommended unless rounded shape and often a “tail” that tracks along the dura dictated by focal findings. outside the brain parenchyma (Figure 32). On noncontrast An MRI typically shows a large, space-occupying lesion images, meningiomas may be hypointense or isointense and with central necrosis, mass effect, and surrounding edema. thus not readily seen. Because of their characteristic MRI Lower-grade gliomas may not enhance. Treatment is usually appearance, many meningiomas are followed clinically, with- resection, if possible, followed by radiation and chemotherapy. out resection or biopsy, unless they are accompanied by Temozolomide, nitrosoureas, and bevacizumab can be used. significant clinical deficits, drug-resistant seizures, severe Prognosis is dependent on pathologic type; 5-year survival headaches, or peritumoral edema. rates for glioblastoma multiforme are less than 10%, and FIGURE 33. MRI showing a right parieto-occipital glioblastoma multiforme. Left, 12-weighted fluid-attenuated inversion recovery sequence shows a heterogeneous intensity mass lesion (/onger yellow arrow) with surrounding hyperintense edema that extends into both hemispheres (shorter yellow arrows). Right, 11-weighted sequence shows a hypointense core suggestive of central necrosis (shorter red arrow) with heterogeneous enhancement (/onger red arrow).

FIGURE 33. MRI showing a right parieto-occipital glioblastoma multiforme. Left, 12-weighted fluid-attenuated inversion recovery sequence shows a heterogeneous intensity mass lesion (/onger yellow arrow) with surrounding hyperintense edema that extends into both hemispheres (shorter yellow arrows). Right, 11-weighted sequence shows a hypointense core suggestive of central necrosis (shorter red arrow) with heterogeneous enhancement (/onger red arrow). 88

Neuro-oncology survival is often measured in months. Prognosis is better in hand, typically do not cause seizures. Gangliogliomas and patients who are younger than 45 years, have an excellent dysembryoplastic neuroepithelial tumors cause medication- functional status, have minimal residual tumor after resection, resistant seizures in more than 90% of patients, and these and receive chemotherapy and radiation after surgery. tumors should be resected, if possible. Seizures may not be directly caused by the CNS tumor but rather by associated conditions or treatment, such as electrolyte disturbances, e Previous exposure to medical therapeutic radiation is infection, chemotherapy, or paraneoplastic encephalitis. the only consistent risk factor for developing gliomas, In patients with CNS tumors not associated with seizures, including glioblastoma multiforme. prophylactic antiepileptic drugs (AEDs) are not recommended, e Prognosis in glioblastoma multiforme is better in although they may be used for 1 week immediately postresec- patients who are younger than 45 years, have an excel- tion. In patients with seizures, older AEDs (phenobarbital, lent functional status, have minimal residual tumor phenytoin, valproic acid, carbamazepine) should be avoided after resection, and receive chemotherapy and radiation because of drug interactions and adverse effects. Levetiracetam after surgery. and lacosamide are preferred because of their lack of drug interactions, IV availability, better tolerability, and rapid titra- Primary Central Nervous System Lymphoma tion to a therapeutic dose. Unprovoked seizures occurring Primary CNS lymphoma (PCNSL) initially occurs without sys- after resection typically require lifelong AED treatment.

survival is often measured in months. Prognosis is better in hand, typically do not cause seizures. Gangliogliomas and patients who are younger than 45 years, have an excellent dysembryoplastic neuroepithelial tumors cause medication- functional status, have minimal residual tumor after resection, resistant seizures in more than 90% of patients, and these and receive chemotherapy and radiation after surgery. tumors should be resected, if possible. Seizures may not be directly caused by the CNS tumor but rather by associated conditions or treatment, such as electrolyte disturbances, e Previous exposure to medical therapeutic radiation is infection, chemotherapy, or paraneoplastic encephalitis. the only consistent risk factor for developing gliomas, In patients with CNS tumors not associated with seizures, including glioblastoma multiforme. prophylactic antiepileptic drugs (AEDs) are not recommended, e Prognosis in glioblastoma multiforme is better in although they may be used for 1 week immediately postresec- patients who are younger than 45 years, have an excel- tion. In patients with seizures, older AEDs (phenobarbital, lent functional status, have minimal residual tumor phenytoin, valproic acid, carbamazepine) should be avoided after resection, and receive chemotherapy and radiation because of drug interactions and adverse effects. Levetiracetam after surgery. and lacosamide are preferred because of their lack of drug interactions, IV availability, better tolerability, and rapid titra- Primary Central Nervous System Lymphoma tion to a therapeutic dose. Unprovoked seizures occurring Primary CNS lymphoma (PCNSL) initially occurs without sys- after resection typically require lifelong AED treatment. temic or lymph node involvement. Its typical pathologic appearance is diffuse large B-cell lymphoma. On MRI, PCNSL ¢ Gangliogliomas and dysembryoplastic neuroepithelial appears as a single, well-demarcated, deep white matter tumors provoke medication-resistant seizures in more (periventricular) lesion with minimal mass effect or edema. than 90% of patients; therefore, patients with these PCNSL evaluation should include HIV testing, lumbar tumors should be referred for resection, if possible. puncture (if not contraindicated because of elevated ICP), and ophthalmologic evaluation with vitreous fluid sampling. e In patients with central nervous system tumors not HVC

temic or lymph node involvement. Its typical pathologic appearance is diffuse large B-cell lymphoma. On MRI, PCNSL ¢ Gangliogliomas and dysembryoplastic neuroepithelial appears as a single, well-demarcated, deep white matter tumors provoke medication-resistant seizures in more (periventricular) lesion with minimal mass effect or edema. than 90% of patients; therefore, patients with these PCNSL evaluation should include HIV testing, lumbar tumors should be referred for resection, if possible. puncture (if not contraindicated because of elevated ICP), and ophthalmologic evaluation with vitreous fluid sampling. e In patients with central nervous system tumors not HVC Lymphomatous cells in vitreous or CSF samples can add to associated with seizures, prophylactic antiepileptic diagnostic sensitivity and may obviate the need for biopsy. drugs are not recommended, although they may be Systemic staging should include bone marrow biopsy, testicu- used for 1 week immediately after resection.

Lymphomatous cells in vitreous or CSF samples can add to associated with seizures, prophylactic antiepileptic diagnostic sensitivity and may obviate the need for biopsy. drugs are not recommended, although they may be Systemic staging should include bone marrow biopsy, testicu- used for 1 week immediately after resection. lar ultrasonography, and whole-body PET or CT. Empiric glu- cocorticoids should be avoided before biopsy because they can Edema and Herniation temporarily suppress lymphoma and prevent or delay a tissue Brain edema can lead to focal neurologic deficits, elevated ICP, diagnosis. or herniation. Brain herniation manifests as an abrupt decline High-dose intravenous (IV) methotrexate combined with in mental status, unreactive dilated pupils, and motor weak- rituximab is the mainstay of treatment and at times is followed ness with flexor or extensor posturing. Emergent treatment to by subsequent radiation. Despite being chemo- and radiosen- prevent death includes elevation of the head of the bed to sitive, PCNSL typically has multiple recurrences and a gener- 30 degrees, hyperventilation (usually with mechanical venti- ally poor prognosis. lation), infusion of either hypertonic saline or mannitol, and administration of glucocorticoids. These treatments can be life-saving and often are used as a bridge to emergent surgery. ¢ Lymphomatous cells in vitreous or cerebral spinal fluid Among glucocorticoids, dexamethasone is preferred because samples may obviate the need for biopsy in diagnosing of its lack of mineralocorticoid effects. Antiangiogenic agents, primary central nervous system lymphoma. such as bevacizumab, can be used as glucocorticoid-sparing e Empiric glucocorticoids should be avoided before agents but take weeks or months to have an effect. biopsy because they can temporarily suppress lym- phoma and prevent or delay a tissue diagnosis.

lar ultrasonography, and whole-body PET or CT. Empiric glu- cocorticoids should be avoided before biopsy because they can Edema and Herniation temporarily suppress lymphoma and prevent or delay a tissue Brain edema can lead to focal neurologic deficits, elevated ICP, diagnosis. or herniation. Brain herniation manifests as an abrupt decline High-dose intravenous (IV) methotrexate combined with in mental status, unreactive dilated pupils, and motor weak- rituximab is the mainstay of treatment and at times is followed ness with flexor or extensor posturing. Emergent treatment to by subsequent radiation. Despite being chemo- and radiosen- prevent death includes elevation of the head of the bed to sitive, PCNSL typically has multiple recurrences and a gener- 30 degrees, hyperventilation (usually with mechanical venti- ally poor prognosis. lation), infusion of either hypertonic saline or mannitol, and administration of glucocorticoids. These treatments can be life-saving and often are used as a bridge to emergent surgery. ¢ Lymphomatous cells in vitreous or cerebral spinal fluid Among glucocorticoids, dexamethasone is preferred because samples may obviate the need for biopsy in diagnosing of its lack of mineralocorticoid effects. Antiangiogenic agents, primary central nervous system lymphoma. such as bevacizumab, can be used as glucocorticoid-sparing e Empiric glucocorticoids should be avoided before agents but take weeks or months to have an effect. biopsy because they can temporarily suppress lym- phoma and prevent or delay a tissue diagnosis. ¢ Emergent treatment, including elevation of the head of

lar ultrasonography, and whole-body PET or CT. Empiric glu- cocorticoids should be avoided before biopsy because they can Edema and Herniation temporarily suppress lymphoma and prevent or delay a tissue Brain edema can lead to focal neurologic deficits, elevated ICP, diagnosis. or herniation. Brain herniation manifests as an abrupt decline High-dose intravenous (IV) methotrexate combined with in mental status, unreactive dilated pupils, and motor weak- rituximab is the mainstay of treatment and at times is followed ness with flexor or extensor posturing. Emergent treatment to by subsequent radiation. Despite being chemo- and radiosen- prevent death includes elevation of the head of the bed to sitive, PCNSL typically has multiple recurrences and a gener- 30 degrees, hyperventilation (usually with mechanical venti- ally poor prognosis. lation), infusion of either hypertonic saline or mannitol, and administration of glucocorticoids. These treatments can be life-saving and often are used as a bridge to emergent surgery. ¢ Lymphomatous cells in vitreous or cerebral spinal fluid Among glucocorticoids, dexamethasone is preferred because samples may obviate the need for biopsy in diagnosing of its lack of mineralocorticoid effects. Antiangiogenic agents, primary central nervous system lymphoma. such as bevacizumab, can be used as glucocorticoid-sparing e Empiric glucocorticoids should be avoided before agents but take weeks or months to have an effect. biopsy because they can temporarily suppress lym- phoma and prevent or delay a tissue diagnosis. ¢ Emergent treatment, including elevation of the head of the bed, hyperventilation, infusion of either hypertonic Medical Management of saline or mannitol, and administration of glucocorti- Complications of Central coids, is necessary to prevent death in patients with

¢ Emergent treatment, including elevation of the head of the bed, hyperventilation, infusion of either hypertonic Medical Management of saline or mannitol, and administration of glucocorti- Complications of Central coids, is necessary to prevent death in patients with Nervous System Tumors brain herniation. Seizures Seizures are more common in low-grade than high-grade Venous Thromboembolism tumors. Tumors near the cortex, especially the temporal lobe Certain characteristics are associated with increased venous or primary motor cortex, are especially associated with sei- thromboembolism risk in patients with CNS tumors (Table 52). zures. White matter and posterior fossa tumors, on the other Despite the risk of intracranial hemorrhage, therapeutic 89

Neuro-oncology may be required. Inferior vena cava filters have considerably TABLE 52. Risk Factors for Venous Thromboembolism in Patients with Central Nervous System Tumors high rates of complications and should be reserved for patients Age >75 years with an absolute contraindication to anticoagulation. Warfarin | or low-molecular-weight heparin may be considered for long- Prolonged immobility or leg weakness | term therapy, although medication interactions between war- | Indwelling vascular catheter farin and chemotherapy or AEDs are a concern. Evidence is Prior venous thromboembolism | insufficient to recommend direct oral anticoagulants for Glioblastoma multiforme patients with CNS tumors. | Glioma>5 cm Prophylactic anticoagulation in combination with mechani- Chemotherapy, particularly hormonal or antiangiogenic agents | cal devices is recommended in hospitalized patients with CNS tumors as soon as possible after resection. Chronic outpatient Recurrent tumor prophylactic anticoagulation is not recommended. Incomplete resection

Chemotherapy, particularly hormonal or antiangiogenic agents | cal devices is recommended in hospitalized patients with CNS tumors as soon as possible after resection. Chronic outpatient Recurrent tumor prophylactic anticoagulation is not recommended. Incomplete resection Immediate postresection period | ¢ Despite the risk of intracranial hemorrhage, therapeutic anticoagulation is generally recommended in confirmed anticoagulation is generally recommended in confirmed venous thromboembolic disease. thromboembolic disease. Anticoagulation has historically e Prophylactic anticoagulation in combination with been avoided in melanoma, choriocarcinoma, papillary thy- mechanical devices is recommended in hospitalized roid carcinoma, and renal carcinoma because of an assumed patients with central nervous system tumors as soon as increased risk of hemorrhage. However, recent studies have possible after resection. not shown that anticoagulation increases hemorrhage risk in patients with these cancers. Besides the usual contraindica- tions, anticoagulation should be avoided in patients with pre- Paraneoplastic/Autoimmune vious intracranial hemorrhage and a platelet count less than 50,000/uL (50 x 10°/L). The presence of a CNS tumor is a Neurologic Syndromes contraindication for thrombolytic therapy in pulmonary Antibody-mediated neurologic syndromes may occur as embolism, although exceptions may be made for low-risk primary autoimmune or paraneoplastic disorders. Various tumors, such as meningiomas. Expert opinion recommends syndromes have been described with different neurologic preanticoagulation neuroimaging with CT to assess for manifestations and findings on serum and CSF studies hemorrhage. (Table 53). Limbic encephalitis is one of the most common Low-molecular-weight heparin is generally preferred presentations and manifests as acute or subacute mood over unfractionated heparin. Exceptions include kidney and behavioral changes, short-term memory problems, impairment and a higher hemorrhage risk when rapid reversal seizures, and cognitive dysfunction; thus, it may appear as

Immediate postresection period | ¢ Despite the risk of intracranial hemorrhage, therapeutic anticoagulation is generally recommended in confirmed anticoagulation is generally recommended in confirmed venous thromboembolic disease. thromboembolic disease. Anticoagulation has historically e Prophylactic anticoagulation in combination with been avoided in melanoma, choriocarcinoma, papillary thy- mechanical devices is recommended in hospitalized roid carcinoma, and renal carcinoma because of an assumed patients with central nervous system tumors as soon as increased risk of hemorrhage. However, recent studies have possible after resection. not shown that anticoagulation increases hemorrhage risk in patients with these cancers. Besides the usual contraindica- tions, anticoagulation should be avoided in patients with pre- Paraneoplastic/Autoimmune vious intracranial hemorrhage and a platelet count less than 50,000/uL (50 x 10°/L). The presence of a CNS tumor is a Neurologic Syndromes contraindication for thrombolytic therapy in pulmonary Antibody-mediated neurologic syndromes may occur as embolism, although exceptions may be made for low-risk primary autoimmune or paraneoplastic disorders. Various tumors, such as meningiomas. Expert opinion recommends syndromes have been described with different neurologic preanticoagulation neuroimaging with CT to assess for manifestations and findings on serum and CSF studies hemorrhage. (Table 53). Limbic encephalitis is one of the most common Low-molecular-weight heparin is generally preferred presentations and manifests as acute or subacute mood over unfractionated heparin. Exceptions include kidney and behavioral changes, short-term memory problems, impairment and a higher hemorrhage risk when rapid reversal seizures, and cognitive dysfunction; thus, it may appear as TABLE 53. Common Autoimmune and Paraneoplastic Neurologic Disorders

Immediate postresection period | ¢ Despite the risk of intracranial hemorrhage, therapeutic anticoagulation is generally recommended in confirmed anticoagulation is generally recommended in confirmed venous thromboembolic disease. thromboembolic disease. Anticoagulation has historically e Prophylactic anticoagulation in combination with been avoided in melanoma, choriocarcinoma, papillary thy- mechanical devices is recommended in hospitalized roid carcinoma, and renal carcinoma because of an assumed patients with central nervous system tumors as soon as increased risk of hemorrhage. However, recent studies have possible after resection. not shown that anticoagulation increases hemorrhage risk in patients with these cancers. Besides the usual contraindica- tions, anticoagulation should be avoided in patients with pre- Paraneoplastic/Autoimmune vious intracranial hemorrhage and a platelet count less than 50,000/uL (50 x 10°/L). The presence of a CNS tumor is a Neurologic Syndromes contraindication for thrombolytic therapy in pulmonary Antibody-mediated neurologic syndromes may occur as embolism, although exceptions may be made for low-risk primary autoimmune or paraneoplastic disorders. Various tumors, such as meningiomas. Expert opinion recommends syndromes have been described with different neurologic preanticoagulation neuroimaging with CT to assess for manifestations and findings on serum and CSF studies hemorrhage. (Table 53). Limbic encephalitis is one of the most common Low-molecular-weight heparin is generally preferred presentations and manifests as acute or subacute mood over unfractionated heparin. Exceptions include kidney and behavioral changes, short-term memory problems, impairment and a higher hemorrhage risk when rapid reversal seizures, and cognitive dysfunction; thus, it may appear as TABLE 53. Common Autoimmune and Paraneoplastic Neurologic Disorders Clinical Presentation Associated Cancers Autoantibody Targets

Immediate postresection period | ¢ Despite the risk of intracranial hemorrhage, therapeutic anticoagulation is generally recommended in confirmed anticoagulation is generally recommended in confirmed venous thromboembolic disease. thromboembolic disease. Anticoagulation has historically e Prophylactic anticoagulation in combination with been avoided in melanoma, choriocarcinoma, papillary thy- mechanical devices is recommended in hospitalized roid carcinoma, and renal carcinoma because of an assumed patients with central nervous system tumors as soon as increased risk of hemorrhage. However, recent studies have possible after resection. not shown that anticoagulation increases hemorrhage risk in patients with these cancers. Besides the usual contraindica- tions, anticoagulation should be avoided in patients with pre- Paraneoplastic/Autoimmune vious intracranial hemorrhage and a platelet count less than 50,000/uL (50 x 10°/L). The presence of a CNS tumor is a Neurologic Syndromes contraindication for thrombolytic therapy in pulmonary Antibody-mediated neurologic syndromes may occur as embolism, although exceptions may be made for low-risk primary autoimmune or paraneoplastic disorders. Various tumors, such as meningiomas. Expert opinion recommends syndromes have been described with different neurologic preanticoagulation neuroimaging with CT to assess for manifestations and findings on serum and CSF studies hemorrhage. (Table 53). Limbic encephalitis is one of the most common Low-molecular-weight heparin is generally preferred presentations and manifests as acute or subacute mood over unfractionated heparin. Exceptions include kidney and behavioral changes, short-term memory problems, impairment and a higher hemorrhage risk when rapid reversal seizures, and cognitive dysfunction; thus, it may appear as TABLE 53. Common Autoimmune and Paraneoplastic Neurologic Disorders Clinical Presentation Associated Cancers Autoantibody Targets Limbic encephalitis,? psychosis, chorea, dysautonomia Ovarian teratoma NMDA receptor®

TABLE 53. Common Autoimmune and Paraneoplastic Neurologic Disorders Clinical Presentation Associated Cancers Autoantibody Targets Limbic encephalitis,? psychosis, chorea, dysautonomia Ovarian teratoma NMDA receptor® Limbic encephalitis,? executive dysfunction, personality SCLC VGKC receptor complex? (includes change, brainstem/limbic encephalitis?, myoclonus, LGI1, CASPR2, contactin-2) | neuropathy, hyponatremia Limbic encephalitis,? brainstem encephalitis, autonomic or SCLC ANNA-1 (Hu) sensory neuropathy Ataxia, brainstem encephalitis Breast cancer, SCLC, gynecologic ANNA-2 (Ri) cancer Ataxia Gynecologic cancer, breast cancer PCA-1 (Yo) Limbic encephalitis,? brainstem encephalitis Testicular cancer Ma1, Ma2 Dementia, personality change, chorea, ataxia, neuropathy SCLC, thymoma CRMP5 Stiff-person syndrome, type 1 diabetes mellitus, ataxia, Thymoma, breast cancer GAD» brainstem encephalitis, ophthalmoplegia, parkinsonism ANNA = antineuronal nuclear antigen; CASPR = contactin associated protein-like; CRMP = collapsin response mediator protein; GAD = glutamic acid decarboxylase; LG| = leucine-rich, glioma inactivated; NMDA = N-methyl-D-aspartate; PCA = Purkinje-cell antibody; SCLC = small cell lung cancer; VGKC = voltage-gated potassium channel. | ?Acute or subacute mood and behavioral changes, short-term memory problems, seizures, and cognitive dysfunction.

ANNA = antineuronal nuclear antigen; CASPR = contactin associated protein-like; CRMP = collapsin response mediator protein; GAD = glutamic acid decarboxylase; LG| = leucine-rich, glioma inactivated; NMDA = N-methyl-D-aspartate; PCA = Purkinje-cell antibody; SCLC = small cell lung cancer; VGKC = voltage-gated potassium channel. | ?Acute or subacute mood and behavioral changes, short-term memory problems, seizures, and cognitive dysfunction. | Not necessarily associated with paraneoplastic syndromes; may be primary autoimmune, without cancer. 90

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Jackson WT, Starling AJ. Concussion Evaluation and Management. Med Clin North Am. 2019;103:251-261. [PMID: 30704680] doi:10.1016/j.mcna. 2018.10.005 e Paraneoplastic/autoimmune limbic encephalitis pre- Mayer A, Quinn D, Master C. The spectrum of mild traumatic brain injury: a sents as acute or subacute mood and behavioral review. Neurology. 2017 Aug 8;89(6):623-32. [PMID: 28701496] doi: 10.1212/ changes, short-term memory problems, seizures, and WNL.0000000000004214. cognitive dysfunction and thus may appear as a rapidly McCrory P, Meeuwisse W, Dvorak J, et al. Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in progressive dementia Berlin, October 2016. BrJ Sports Med. 2017;51:838-847. [PMID: 28446457] doi:10.1136/bjsports-2017-097699 e In suspect cases, the patient should be thoroughly eval- Mullally WJ. Concussion. Am J Med. 2017;130:885-92. [PMID: 28502817]. doi: uated for an antibody-mediated process and for sys- 10.1016/j.amjmed.2017.04.016. temic cancer, which sometimes includes surveillance Seizures and Epilepsy that continues for years after the primary syndrome is Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of diagnosed. convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16:48-61. [PMID: 26900382] doi:10.5698/1535-7597-16.1.48. Gynecologic management of adolescents and young women with seizure dis- Bibliography orders: ACOG committee opinion, number 806. Obstet Gynecol. 2020; 135:e213-20. [PMID: 32332416] Headache and Facial Pain Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task Force American Headache Society. The American Headache Society Position of the American Clinical Neurophysiology Society. Consensus statement on Statement On Integrating New Migraine Treatments Into Clinical Practice. continuous EEG in critically ill adults and children, part I: indications. J Headache. 2019;59:1-18. [PMID: 30536394] doi:10.1111/head.13456 Clin Neurophysiol. 2015;32:87-95. [PMID: 25626778] Burch R. Migraine and tension-type headache. Med Clin N Am 2019 Mar; Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: 103(2):215-33. [PMID: 30704678] doi: 10.1016 /j.mcna.2018.10.003. efficacy and tolerability of the new antiepileptic drugs I: treatment of new- Diener HC, Dodick D, Evers S, et al. Pathophysiology, prevention, and treat- onset epilepsy: report of the Guideline Development, Dissemination, and ment of medication overuse headache. Lancet Neurol. 2019;18:891-902. Implementation Subcommittee of the American Academy of Neurology and [PMID: 31174999] doi:10.1016/S1474-4422(19)30146-2 the American Epilepsy Society. Neurology. 2018;91:74-81. [PMID: 29898971] Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the Treatment of Kapur J, Elm J, Chamberlain JM, et al; NETT and PECARN Investigators. Migraine. N Engl J Med. 2019;381:2230-2241. [PMID: 31800988] doi:10.1056/ Randomized trial of three anticonvulsant medications for status epilepti- NEJMoal1813049 cus. N EnglJ Med. 2019;381:2103-13. [PMID: 31774955] Ferro JM, Coutinho JM, Dentali F, et al. Safety and efficacy of dabigatran etex- Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: ilate vs dose-adjusted warfarin in patients with cerebral venous thrombo- Management of an unprovoked first seizure in adults: report of the sis: a randomized clinical trial [published online ahead of print, 2019 Sep Guideline Development Subcommittee of the American Academy of 3]. JAMA Neurol. 2019;76 (12):1457-1465. doi:10.1001/jamaneurol.2019.2764 Neurology and the American Epilepsy Society. Neurology. 2015;84:1705-13. Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster [PMID: 25901057] headache. Lancet Neurol. 2018;17:75-83. [PMID: 29174963] doi:10.1016/ Pack AM. Epilepsy Overview and revised classification of seizures and epilep- $1474-4422(17)30405-2 sies. Continuum (Minneap Minn). 2019;25:306-21. [PMID: 30921011] Jensen RH. Tension-Type Headache - The Normal and Most Prevalent Sazgar M. Treatment of women with epilepsy. Continuum (Minneap Minn). Headache. Headache. 2018;58:339-345. [PMID: 28295304] doi:10.1111 2019 Apr;25(2):408-30. doi: 10.1212/CON.0000000000000713. Review. head.13067 PubMed PMID:30921016.

cognitive dysfunction and thus may appear as a rapidly McCrory P, Meeuwisse W, Dvorak J, et al. Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in progressive dementia Berlin, October 2016. BrJ Sports Med. 2017;51:838-847. [PMID: 28446457] doi:10.1136/bjsports-2017-097699 e In suspect cases, the patient should be thoroughly eval- Mullally WJ. Concussion. Am J Med. 2017;130:885-92. [PMID: 28502817]. doi: uated for an antibody-mediated process and for sys- 10.1016/j.amjmed.2017.04.016. temic cancer, which sometimes includes surveillance Seizures and Epilepsy that continues for years after the primary syndrome is Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of diagnosed. convulsive status epilepticus in children and adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16:48-61. [PMID: 26900382] doi:10.5698/1535-7597-16.1.48. Gynecologic management of adolescents and young women with seizure dis- Bibliography orders: ACOG committee opinion, number 806. Obstet Gynecol. 2020; 135:e213-20. [PMID: 32332416] Headache and Facial Pain Herman ST, Abend NS, Bleck TP, et al; Critical Care Continuous EEG Task Force American Headache Society. The American Headache Society Position of the American Clinical Neurophysiology Society. Consensus statement on Statement On Integrating New Migraine Treatments Into Clinical Practice. continuous EEG in critically ill adults and children, part I: indications. J Headache. 2019;59:1-18. [PMID: 30536394] doi:10.1111/head.13456 Clin Neurophysiol. 2015;32:87-95. [PMID: 25626778] Burch R. Migraine and tension-type headache. Med Clin N Am 2019 Mar; Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: 103(2):215-33. [PMID: 30704678] doi: 10.1016 /j.mcna.2018.10.003. efficacy and tolerability of the new antiepileptic drugs I: treatment of new- Diener HC, Dodick D, Evers S, et al. Pathophysiology, prevention, and treat- onset epilepsy: report of the Guideline Development, Dissemination, and ment of medication overuse headache. Lancet Neurol. 2019;18:891-902. Implementation Subcommittee of the American Academy of Neurology and [PMID: 31174999] doi:10.1016/S1474-4422(19)30146-2 the American Epilepsy Society. Neurology. 2018;91:74-81. [PMID: 29898971] Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the Treatment of Kapur J, Elm J, Chamberlain JM, et al; NETT and PECARN Investigators. Migraine. N Engl J Med. 2019;381:2230-2241. [PMID: 31800988] doi:10.1056/ Randomized trial of three anticonvulsant medications for status epilepti- NEJMoal1813049 cus. N EnglJ Med. 2019;381:2103-13. [PMID: 31774955] Ferro JM, Coutinho JM, Dentali F, et al. Safety and efficacy of dabigatran etex- Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: ilate vs dose-adjusted warfarin in patients with cerebral venous thrombo- Management of an unprovoked first seizure in adults: report of the sis: a randomized clinical trial [published online ahead of print, 2019 Sep Guideline Development Subcommittee of the American Academy of 3]. JAMA Neurol. 2019;76 (12):1457-1465. doi:10.1001/jamaneurol.2019.2764 Neurology and the American Epilepsy Society. Neurology. 2015;84:1705-13. Hoffmann J, May A. Diagnosis, pathophysiology, and management of cluster [PMID: 25901057] headache. Lancet Neurol. 2018;17:75-83. [PMID: 29174963] doi:10.1016/ Pack AM. Epilepsy Overview and revised classification of seizures and epilep- $1474-4422(17)30405-2 sies. Continuum (Minneap Minn). 2019;25:306-21. [PMID: 30921011] Jensen RH. Tension-Type Headache - The Normal and Most Prevalent Sazgar M. Treatment of women with epilepsy. Continuum (Minneap Minn). Headache. Headache. 2018;58:339-345. [PMID: 28295304] doi:10.1111 2019 Apr;25(2):408-30. doi: 10.1212/CON.0000000000000713. Review. head.13067 PubMed PMID:30921016. 91