Neurological Differential Diagnosis - part 7 pptx

322 Chapter 9 Features Peripheral vertigo Central vertigo Latency (time to onset of vertigo and nystagmus) 0–40 seconds (average 7–8 seconds) No latency Begins immediately Fatigability (lessening signs and symptoms after repetitive maneuvers) Ye s N o Nystagmus Direction fi xed, torsional, up, upper poles of eyes toward the ground Direction changing, variable Reproducibility Less consistent More consistent 323 Chapter 10 Neuro-oncology General information 324 Epidemiology 324 Frequency of primary CNS neoplasms by type 324 Specifi c histological types 325 WHO classifi cation of gliomas 325 Pilocytic astrocytomas: location 326 Malignant astrocytomas: location and presenting symptoms 327 Ependymomas: presenting symptoms 328 Meningiomas: location and cranial nerve symptoms 328 Intracranial metastases 329 Circumscribed, noninfi ltrating brain tumors 331 Differentials (in order of frequency) 331 By age and location 331 Common brain tumor types by location and age 331 Supratentorial tumors: adult 333 Infratentorial tumors: pediatric and adult 335 Tumors in particular brain regions 337 Sellar/suprasellar tumors 337 Pineal region tumors 338 Intraventricular tumors 338 Cerebellopontine angle tumors 338 Spinal cord tumors 338 Spinal cord: intra- vs. extramedullary tumors 339 Spinal cord: primary intramedullary tumors 340 Spinal cord: tumors by age and location 340 Associated syndromes 341 Paraneoplastic syndromes 341 Leptomeningeal carcinomatosis 343 Neoplasms causing endocrinopathies 343 Neurological complications of cancer therapies 344 Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri, Michael F. Waters, Christopher C. Giza, Copyright © 2005 Roongroj Bhidayasiri, Michael F. Waters and Christopher C. Giza 324 Chapter 10 General information Epidemiology Frequency of primary CNS neoplasms by type Histological type Children Adults Astrocytoma 25–33% 10–15% Glioblastoma 3–5% 20–25% Medulloblastoma 18–19% – Meningioma – 20–30% • Primary CNS neoplasms are classifi ed histologically based on the presumed normal CNS cell type. • In some neoplasms, the cell-of-origin remains unknown. • Frequently, a neoplasm is a mixture of different cell types. • Primary CNS tumors rarely metastasize outside the CNS. • Morbidity in intracranial tumors is principally a feature of expansion of intracranial contents within a closed space. In severe cases, this leads to herniation and compression of the respiratory drive center. • Determination of malignancy is generally based on fi ve histological features: ◆ nuclear atypia, ◆ cellular pleomorphism, ◆ mitoses, ◆ vascular proliferation, and ◆ necrosis • Approximately 85% are intracranial, and 15% spinal • Cumulatively, astrocytomas (combining astrocytomas and glioblastoma multiforme) represent about 30% of intracranial tumors in adults. The majority (70%) of gliomas in adults are supratentorial. • By contrast, in children, glioblastoma is rare, but astrocytomas are very common (up to 48% of some series). Common pediatric astrocytoma variants include the brainstem astrocytoma and the pilocytic astrocytoma. Medulloblastomas (44%) and ependymomas (8%) are also more frequent in children. The majority of pediatric gliomas (70%) are infratentorial. • Primary CNS lymphoma has increased in incidence, particularly in persons with impaired immunity (HIV, organ transplant recipients, other immunodefi ciency states). Neuro-oncology 325 Histological type Children Adults Ependymoma 5–7% 2% Craniopharyngioma 3–6% – Pituitary 1–10% 4–8% Nerve sheath tumor – 2–7% Oligodendroglioma 2–4% 4% Germ cell tumor 3–7% – Lymphoma – 2–3% Others 25–30 10–12% ‘–’ signifi es <2%. Modifi ed from Schoenberg B.S., et. al., Mayo Clin Proc 51: 51–56, 1976 and Rowland, Merritt’s Textbook of Neurology, 9th edition, 1995. Specifi c histological types WHO classifi cation of gliomas 1 Astrocytic tumors: 1.1 Astrocytoma 1.1.1 Fibrillary 1.1.2 Protoplasmic 1.1.3 Gemistocytic 1.2 Anaplastic (malignant) astrocytoma 1.3 Glioblastoma 1.3.1 Giant cell 1.3.2 Gliosarcoma 1.4 Pilocytic astrocytoma 1.5 Pleomorphic xanthoastrocytoma 1.6 Subependymal astrocytoma • Gliomas represent the most frequently encountered primary CNS neoplasms. • They may cause pathology via widespread paranchymal invasion (diffuse gliomas) or compressive mass effect (ependymomas). • Gliomas demonstrate anaplastic transformation, defi ned as the tendency to become increasingly malignant over time. • They histologic classifi cation is frequently complicated by a tendency toward heterogeneous composition. 326 Chapter 10 2 Oligodendroglial tumors: 2.1 Oligodendroglioma 2.2 Anaplastic (malignant) oligodendroglioma 3 Ependymal tumors: 3.1 Ependymoma 3.1.1 Cellular 3.1.2 Capillary 3.1.3 Clear cell 3.2 Anaplastic (malignant) ependymoma 3.3 Myxopapillary ependymoma 3.4 Subependymoma 4 Mixed gliomas: 4.1 Oligo-astrocytoma 4.2 Anaplastic (malignant) oligo-astrocytoma 4.3 Others Pilocytic astrocytomas: location Location Frequency Cerebral ~32% Basal ganglia/thalamus ~21% Cerebellum ~20% Brainstem ~12% Modifi ed from Greenberg H.S., Chandler W.F., and Sandler H.M., Brain Tumors, 1999. • Peak incidence is 10 years old with ~80% occurrence in 1st two decades. • Often midline, occurring in the thalamus, hypothalamus, cerebellum, optic chiasm, and brainstem. • Clinical symptoms related to location. Neurological signs and symptoms progress slowly (in the absence of obstructive hydrocephalus). Symptoms include: headache (50%), seizures (50%), visual changes (20%), and weakness (20%). Signs include: papilledema, hemianopsia, and weakness. • Most common astrocytic cerebellar neoplasm in children. • Relatively benign, with excellent prognosis if surgical resection is possible. Neuro-oncology 327 Malignant astrocytomas: location and presenting symptoms Location of tumor % Frontal ~20 Temporal ~17 Parietal ~15 Occipital ~3 Symptom ~% initial symptoms ~% at presentation for medical care Headache 38 78 Seizure 18 30 Weakness 8 43 Altered mental status 7 42 Dysphagia 5 30 Visual changes 4 39 Altered level of consciousness 2 36 Sensory disturbance 2 14 Gait disturbance 1.5 19 Nausea/emesis 33 Modifi ed from Greenberg H.S., Chandler W.F., and Sandler H.M., Brain Tumors, 1999. • Classifi ed by the World Health Organization (WHO) by increasing malignancy as: ◆ low-grade astrocytoma (grade II), ◆ anaplastic astrocytoma (grade III), and ◆ glioblastoma (grade IV) • The most common adult brain tumor, ~30–45% of primary brain tumors. • More common in men than in women. • More common in whites than in blacks. • Genetic factors in glioblastoma multiforme include loss of chromosome 10 and duplication of epidermal growth factor receptor gene (EGFR) on chromosome 7. • Prognosis generally poor for grade III and grade IV tumors. 328 Chapter 10 Ependymomas: presenting symptoms Symptom % of patients reporting early % of patients re- porting at diagnosis Nausea/emesis 29 100 Headache 33 86 Dizziness 9 43 Diplopia 5 48 Gait ataxia 5 48 Hemiparesis 5 9 Modifi ed from Rawlings et al., Surgical Neurol 29: 272–281, 1988. Meningiomas: location and cranial nerve symptoms Attachment % of meningiomas Parasagittal and falx cerebri 25 Convexity 20 Sphenoid ridge 20 Continued • Ependymomas account for approximately 5% of all intracranial tumors, though in children they are the third most common intracranial neoplasm. • Ependymomas account for 33% of intracranial neoplasms in children younger than 3 years. • Ependymomas account for 67% of all spinal intramedullary and intradural tumors. • Can occur in any portion of the ventricular system, including the spinal central canal, although they occur in greatest frequency in the fourth ventricle. • Hydrocephalus frequently develops and often accounts for initial symptoms. • Meningiomas are classifi ed by their site of attachment. • Due to their tendency to extend, cranial nerve pathology may or may not accurately predict actual primary meningioma location. Neuro-oncology 329 Attachment % of meningiomas Olfactory groove 10 Suprasellar 10 Posterior fossa 10 Middle fossa 3 Intraventricular 2 Attachment Common CN affected Signs & symptoms Inner sphenoid ridge VI, III, IV, V 1 Visual loss, optic atrophy Olfactory groove I, II Anosmia, visual loss, altered mental status, seizures Cavernous sinus II, IV, VI, V 1 , V 2 Occulomotor pathology, facial sensory disturbances Cerebellopontine angle V, VII, VIII, IX, X Tinnitus, vertigo, facial paralysis, cerebellar pathology, brainstem signs Middle and rostral clivus III, V, VI, VII, VIII Multiple Posterior clivus IX, X, XI, XII Multiple Cerebellar convexity/tentorium None Cerebellar signs, visual loss/ hemianopia Foramen magnum VIII, IX, X, XI, XII Cervical and upper extremity sensory disturbances and weakness Modifi ed from Hildebrand J., and Brada M., Differential Diagnosis in Neuro-oncology, 2001. Intracranial metastases • Metastasis may occur to brain parenchyma, to dura, or to leptomeninges. Different types of tumors metastasize preferentially to these locations. • Up to 25% of patients with systemic cancer develop metastases to one of these locations. • Parenchymal metastases are usually multifocal and located preferentially near the gray-white junction. • Dural metastasis is distinct from leptomeningeal metastasis. • Leptomeningeal metastasis is defi ned as neoplastic invasion of the pia mater and arachnoid. • Occurs in approximately 5% of all cancer patients. • Typically due to hematogenous spread, but may also occur via direct invasion from vertebral metastases, shedding in the CNS, and invasion of nerve sheaths. Iatrogenic metatases may occur after surgical resection. • Clinical manifestations are extremely variable and frequently multifocal. 330 Chapter 10 Metastatic tumors to the brain (sites of primary neoplasm) % Lung 46% Breast 13% GI 9% Leukemia 7% GU 7% Upper respiratory tract 3% Melanoma 3% Sarcoma 3% Others (liver, endocrine, pancreas, etc.) 9% ◆ Most common parenchymal metastases ■ Lung ■ Melanoma ■ Breast ■ Renal ■ Lymphoma ■ Prostate rarely metastasizes to brain ◆ Most common dural metastases ■ Prostate ■ Breast ■ Some sarcomas ◆ Most common leptomeningeal metastases ■ Breast (~41%) ■ Lung (~32%) ■ Skin (includes melanoma) (~10%) ■ GI (~5.5%) ■ GU (~4.5%) ◆ Most common hemorrhagic metastases ■ Lung ■ Renal ■ Choriocarcinoma ■ Melanoma ◆ Primary CNS tumors that ‘metastasize’ within the CNS ■ Glioblastoma ■ Medulloblastoma • Diagnosis should include CSF studies with cytometry (for meningeal metastasis) and imaging (for all types of metastasis). • Solitary brain metastasis is a term used to signify cases when no other bodily metastasis (in or out of the brain) is known. Neuro-oncology 331 ■ Choroid plexus papilloma ■ Ependymoma ■ Less common (meningioma, germinoma, pineoblastoma) Circumscribed, noninfi ltrating brain tumors 1 Metastasis ◆ Typically show a sharp ‘pushing’ interface with brain parenchyma. ◆ Often multiple, located at gray-white junction. 2 Meningioma ◆ Well-circumscribed, fi rmly attached to dura and may involve adjacent bone. ◆ Exert symptoms by compressing adjacent structures, including cranial and peripheral nerve roots. 3 Central neurocytoma and subependymoma ◆ Both tumors grow exophytically into the ventricles. 4 Plemorphic xanthoastrocytoma ◆ One of the ‘circumscribed’ astrocytic neoplasms. 5 Infectious lesions: brain abscesses and granulomas may occasionally mimic these types of tumors. Differentials (in order of frequency) By age and location Common brain tumor types by location and age The top three tumors by location are listed below Pediatric tumors 1 Cerebral hemisphere 1.1 Astrocytoma 1.2 Ependymoma • Most primary brain tumors, including gliomas and lymphomas, diffusely infi ltrate the brain parenchyma. • A few varieties of neoplasm are well-circumscribed and do not generally invade brain parenchyma. • Location of primary CNS tumors is predictive of tumor type. • Predictive tumor type by location is also infl uenced by patient age. [...]... dysfunction 3 67 Infantile hypotonia 3 67 Common causes of persistent toe walking in children 370 Ataxia 370 Dizziness/vertigo in children 370 Ataxia in children 371 345 Headache in children 374 Acute headache presentation (more likely at emergency department or urgent care clinic) 375 Chronic headache presentation (more likely at clinic) 376 Neoplasms (see Chapter 10: Neuro-oncology) Visual disturbances 377 Visual... polyneuropathy Anti-Yo (PCA-1) Gynecological, breast Cerebellar degeneration Anti-Ri (adult) Small cell lung carcinoma, gynecological, breast Cerebellar ataxia, opsoclonus Anti-Ri (pediatric) Neuroblastoma Opsoclonus-myoclonus Anti-Ma1 Many Cerebellar degeneration, brainstem dysfunction Anti-Ma2 Testicular Limbic encephalitis Anti-Tr Hodgkin lymphoma Cerebellar degeneration Anti-CV2 (CRMP-5) Small cell... degeneration, encephalomyelitis, peripheral neuropathy Anti-voltage-gated calcium channel (VGCC) Small cell lung carcinoma Lambert-Eaton syndrome Anti-amphiphysin Breast, small cell lung carcinoma Stiff-person syndrome, encephalomyelitis Anti-PCA-2 Small cell lung carcinoma Cerebellar degeneration, encephalomyelitis, Lambert-Eaton syndrome ANNA-3 Lung cancer Sensory neuropathy, encephalomyelitis Leptomeningeal... presentation (more likely at clinic) 376 Neoplasms (see Chapter 10: Neuro-oncology) Visual disturbances 377 Visual loss in children: neurological causes 377 Nystagmus in infants 378 Other 378 Guidelines for the determination of brain death in children 378 Macrocephaly 379 Nightmares vs night terrors 381 Paroxysmal disorders and seizures Paroxysmal disorders Paroxysmal disorders in infants/toddlers •... urinary incontinence, optic atrophy, cataracts Focal radiation-induced leukoencephalopathy, myelopathy (early- and late-delayed), brachial and lumbosacral plexopathies, focal peripheral neuropathies * Do not give methotrexate following radiation therapy Focal radiation, methotrexate Diffuse radiation, methotrexate Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri, Michael... (upgaze paralysis, light-near dissociation), lid retraction Endocrine dysfunction (5%): diabetes insipidus, precocious puberty ■ ■ ■ Neuro-oncology 335 8 Pineal cell tumors ◆ Occur predominantly motor peripheral neuropathy Guillain-Barré-like syndrome Headache, nausea, somnolence, late-onset leukoencephalopathy (6 months to years) with cognitive... Neonatal seizures: etiology, p 3 57 1.1 Tonic seizures with or without apnea: particularly in premies 1.2 Tonic eye deviation 1.3 Focal clonic jerks 1.4 Multifocal clonic jerking 1.5 Myoclonic jerks 1.6 Benign familial neonatal seizures: AD Rare; family history may not be evident until relatives interviewed Diagnosis of exclusion, does NOT preclude work-up for other causes 1 .7 Ohtahara syndrome Rare catastrophic... Progressive myoclonus epilepsies Clinical characteristics: myoclonus, seizures (tonic-clonic, tonic, or myoclonic), progressive dementia, and ataxia 3.9 Lennox-Gastaut syndrome (see Lennox-Gastaut syndrome DDx, pp 354– 5) 3.10 Rasmussen syndrome (see Epilepsia partialis continua DDx, pp 355–6) 3.11 Acquired epileptiform aphasia/Landau-Kleffner syndrome Onset usually in childhood Loss of previously acquired language . loss ( 97% ), tinnitus (70 %), and gait unsteadi- ness (70 %) are common. Other common signs/symptoms include headache (38%), nystagmus (34%), and facial numbness (33%). Neuro-oncology 3 37 4 Ependymoma ◆ . carcinomatosis 343 Neoplasms causing endocrinopathies 343 Neurological complications of cancer therapies 344 Neurological Differential Diagnosis: A Prioritized Approach Roongroj Bhidayasiri,. states). Neuro-oncology 325 Histological type Children Adults Ependymoma 5 7% 2% Craniopharyngioma 3–6% – Pituitary 1–10% 4–8% Nerve sheath tumor – 2 7% Oligodendroglioma 2–4% 4% Germ cell tumor 3 7% – Lymphoma