CNS Part 2 PDF - Central Nervous System Diseases

# Department of Pathology ## The Central Nervous System (CNS) ### Part 2 Mark Lester Dalanon, MD Lecturer October 24, 2023 [email protected] # OUTLINE ## 01 Diseases of the CNS - Demyelinating Diseases - Multiple Sclerosis - Neuromyelitis Optica - Central Pontine Myelinolysis - T...

# Department of Pathology ## The Central Nervous System (CNS) ### Part 2 Mark Lester Dalanon, MD Lecturer October 24, 2023 [email protected] # OUTLINE ## 01 Diseases of the CNS - Demyelinating Diseases - Multiple Sclerosis - Neuromyelitis Optica - Central Pontine Myelinolysis - Tumors - Gliomas - Choroid Plexus Tumor - Primary CNS Lymphoma - Meningioma - Familial Tumor Syndromes - Metastatic Tumors ## 02 Review Questions ## 03 Reading Assignment ## Toxic and Acquired Metabolic Disease - Vitamin Deficiencies - Neurologic Sequelae of Metabolic Disturbance - Toxic Disorders ## Neurodegenerative Diseases - Prions - Alzheimer's Disease - Parkinson's Disease - Huntington's Disease - Amyotrophic Lateral Sclerosis # 02 Diseases of the Central Nervous System ## Disease of the CNS - Cerebral Edema, Hydrocephalus, Raised Intracranial Pressure & Herniation - Congenital Anomalies - Trauma & Infection - Demyelinating and Neurodegenerative Disease - Cerebrovascular Disease - Tumors - Toxic and Acquired Metabolic Disease # 02 Demyelinating diseases of the CNS Acquired conditions characterized by preferential damage to myelin with relative preservation of axons Clinical deficits are due to the effect of myelin loss on the transmission of electrical impulses along axons Pathologic processes that can cause loss of myelin. - Immune-mediated destruction of myelin - i.e. Multiple Sclerosis - Infections - i.e Progressive Multifocal Leukoencephalopathy (PML) - Inherited disorders - Leukodystrophies - Affect synthesis or turnover of myelin components # 02 Multiple Sclerosis (MS) Autoimmune demyelinating disorder characterized by distinct episodes of neurologic deficits Most common of the demyelinating disorders (approximately 1 per 1000 persons) Onset in childhood or after 50 years of age is relatively rare Women are affected twice compared to men Lesions can occur anywhere in the CNS and consequently may induce a wide range of clinical manifestations - Optic neuritis - Visual impairment due to involvement of the optic nerve is a frequent initial manifestation - Brainstem involvement produces cranial nerve signs such as ataxia, nystagmus, and internuclear ophthalmoplegia - Spinal cord lesions give rise to motor and sensory impairment of extremities, spasticity, and loss of bladder control # 02 Multiple Sclerosis (MS) - CSF examination shows a mildly elevated protein level and moderate pleocytosis (1/3 of cases) - Gross Finding - Lesion is firmer than the surrounding white matter ("sclerosis") - Well circumscribed, depressed, glassy, gray-tan, irregularly shaped plaques - Microscopic Finding - Active demyelinating plaques appear very cellular - Presence of numerous lipid-laden macrophages # 02 Multiple Sclerosis (MS): Immunopathogenesis - Pre-existing autoreactive T-cells - Peripheral activation - Adhesion & migration into CNS - Local activation & proliferation - T cells are reactivated on encountering local CNS antigens via an Interaction with antigen-presenting cells # 02 Neuromyelitis Optica (NMO) Syndrome with synchronous bilateral optic neuritis and spinal cord demyelination Greater skewing toward women than MS Presence of aquaporin-4 antibodies (AQP4 IgG) - aquaporin-4 (AQP4) is the major water channel of astrocytes - Demyelination in NMO show loss of aquaporin-4 - Acute attacks are treated with glucocorticoids or plasma exchange - Long-term treatments include agents that decrease antibody titers or inhibit complement # 02 Central Pontine Myelinolysis Clinically known as Osmotic Demyelination Syndrome Acute disorder characterized by loss of myelin in the base of the pons (basis pontis) and portions of the pontine tegmentum Rapid increase in osmolality damages the oligodendrocytes through uncertain mechanisms Arises 2 to 6 days after rapid correction of hyponatremia # 02 Neurodegenerative Diseases Disorders characterized by the progressive loss of particular groups of neurons, which often have shared functions Accumulation of protein aggregates ("proteinopathy") Varles with respect to the anatomic localization of Involved areas and their specific cellular abnormalities Can be classified using two different approaches: - Symptomatic/Anatomic - Based on the anatomic regions that are most affected - Which is typically reflected in the clinical symptoms - (e.g., neocortical involvement results in cognitive impairment and dementia) - Pathologic - Based on the types of inclusions or abnormal structures observed - (e.g., diseases with inclusions containing tau or containing synuclein) # 02 Features of the Major Neurodegenerative Diseases | Disease | Clinical Pattern | Inclusions | Genetic Causes | |---|---|---|---| | Prion diseases | Rapidly progressive dementia | Kuru plaques and diffuse PrP deposits | PrP | | Alzheimer disease (AD) | Dementia | Aẞ (plaques) and tau (tangles) | APP, PS-1, PS-2, trisomy 21 | | Frontotemporal lobar degeneration (FTLD) | Behavioral changes, language disturbance | TDP-43 | TDP-43, progranulin, C9orf72 | | Parkinson discase (PD) | Hypokinetic movement disorder with or without dementia | FUS | FUS | | | | a-synuclein | a-synuclein (mutations or amplification) | | | | α-synuclein or none | LRRK2 | | | | | DJ-1, PINK 1, parkin | | Progressiva supranuclear palsy (PSP) | Parkinsonism with abnormal eye movements | tau | tau | | Corticobasal degeneration (CBD) | Parkinsonism with asymmetric movement disorder | tau | tau | | Multiplo system atrophy (MSA) | Parkinsonism, cerebellar ataxia, autonomic failure | a-synuclein | | | Huntington disease (HD) | Hyperkinetic movement disorder | Huntington (polyglutamine) | Htt | | Spinocerebellar ataxias (SCA-1, 2, 3, 6, 7, 17 and DRPLA) | Cerebellar ataxia | Various proteins (polyglutamine containing) | Multiple loci | | Amyotrophic lateral sclerosis (ALS) | Weakness with upper and lower motor neurons signs | SOD1 | SOD1 | | | | TDP-43 | TDP-43, C9orf72 | | | | FUS | FUS | | Spinal bulbar muscular atrophy (SBMA) | Lower motor neuron weakness, diminished androgen | Androgen receptor (polyglutamine containing) | Androgen receptor | # 02 Relationship Between Proteins and Neurodegenerative Diseases | Protein | Diseases With Inclusions | |---|---| | Aẞ | Alzheimer disease | | tau | Alzheimer disease | | AfPaPa CC | Frontotemporal lobar degeneration | | | Parkinson disease (with LRRK2 mutations) | | | Progressive supranuclear palsy | | | Corticobasal degeneration | | | Chronic traumatic encephalopathy | | | Frontotemporal lobar degeneration | | | Amyotrophic lateral sclerosis | | TPD-43 | Frontotemporal lobar degeneration | | | Amyotrophic lateral sclerosis | | FUS | Frontotemporal lobar degeneration | | | Amyotrophic lateral sclerosis | | a-synuclein | Parkinson disease | | | Multiple system atrophy | | Polyglutamine aggregates (different protein in each disease) | Huntington disease | | | Some forms of spinocerebellar ataxia | | | Spinal bulbar muscular atrophy | # 02 Prion Diseases Rapidly progressive neurodegenerative disorders caused by aggregation and intercellular spread of a misfolded prion protein (PrP) May be sporadic, familial, or transmitted Exemplify degenerative disorders that are caused by "spreading" of misfolded proteins Examples of Prion diseases include: - Creutzfeldt-Jakob disease (CJD) - Gerstmann-Sträussler-Scheinker syndrome - Fatal Familial Insomnia - Kuru (Human) - Scrapie - Bovine Spongiform Encephalitis (BSE) All of these diseases are characterized morphologically by "spongiform change" - intracellular vacuoles in neurons and glia Cinically by a rapidly progressive dementia # 02 Prion Diseases - Creutzfeldt-Jakob Disease (CJD) - The most common prion disease - A rare disorder that manifests as a rapidly progressive dementia - Sporadic form has an annual incidence of approximately 1 per 1,000,000 - Accounts for 90% of cases - Familial forms are caused by mutations in PRNP, the gene that encodes PrP (prion protein) - Symptoms - Onset shows subtle changes in memory and behavior - Followed by a rapidly progressive dementia often associated with starde myoclonus - startled muscle jerks - Uniformly fatal - Average survival of 7 months after the onset of symptoms # 02 Alzheimer Disease (AD) Most common cause of dementia in older adults Incidence of the disease increases with age & prevalence roughly doubles every 5 years - 1% for the 60 to 64 year old - Reaching 40% or more for 85 to 89 year old Signs and Symptoms - Starts as an insidious impairment of higher cognitive functions - Deficits in memory, visuospatial orientation, judgment, personality, and language gradually emerge - In 5 to 10 years, affected individual becomes profoundly disabled, mute, and immobile # 02 Alzheimer Disease (AD) Accumulation of two proteins (Aẞ and tau) in specific brain regions Likely as a result of excessive production and defective removal Two pathologic hallmarks - Amyloid plaques - deposits of aggregated Aẞ peptides in the neuropil - Neurofibrillary tangles - aggregates of the microtubule binding protein tau - develop intracellularly and persist extracellularly after neuronal death # 02 Alzheimer Disease (AD) - Damaged mitochondria, Oxidative stress - Aß dimers in the claft - AD pathology - NFT (Tau aggregates) - Neuronal loos - Amyloid plaquos - APP gene mutation - Microbiome - APP Imbalance in production and clearance # 02 Parkinson Disease (PD) Neurodegenerative disease marked by a hypokinetic movement disorder caused by loss of dopaminergic neurons from the substantia nigra pars compacta - pars basalie is another part Clinical syndrome of Parkinsonism - Diminished facial expression (Masked facies) - Stooped posture - Slowing of voluntary movement - Festinating gait (progressively shortened, accelerated steps) - Rigidity - "Pill-rolling" tremor Clinical diagnosis of PD - Based on Triad of Parkinsonism-tremor, rigidity, and bradykinesia - Absence of a toxic or other known underlying etiology # 02 Parkinson Disease (PD) Associated with protein accumulation and aggregation, mitochondrial abnormalities, and neuronal loss in the substantia nigra - SNCA gene - encodes a-synuclein, an abundant lipid-binding protein normally localized to synapse - Major component of the Lewy body (diagnostic hallmark of PD) - Mitochondrial dysfunction - mutations in genes that encode the proteins DJ-1, PINK1, and parkin - Mutations LRRK2 (leucine-rich repeat kinase 2) - most common cause of autosomal dominant PD - are also found in some late-onset and sporadic cases of the disease # 02 Huntington Disease (HD) Autosomal dominant disease caused by degradation of striatal neurons Characterized by a progressive movement disorder and dementia Signs & Symptoms - Jerky, hyperkinetic, and dystonic movements involving all parts of the body (chorea)) - Later develop bradykinesia and rigidity - Relentlessly progressive and uniformly fatal - Average course of about 15 years # 02 Huntington Disease (HD) Prototypic polyglutamine trinucleotide repeat expansion disease - HTT gene - located on chromosome 4p16.3 - encodes a 348-kD protein known as huntingtin - Stretch of CAG repeats that encodes a polyglutamine region - Gross Findings - Brain is small and shows striking atrophy of the caudate nucleus and the putamen, dorsal striatum - Lateral and third ventricles are dilated - Microscopic examination - Profound loss of striatal neurons - Protein aggregates containing huntingtin in the neuron # 02 Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig's Disease Progressive disorder with loss of upper motor neurons in the cerebral cortex and lower motor neurons in the spinal cord and brainstem Results in denervation of muscles leading to weakness that becomes profound as the disease progresses Overall incidence of 2 per 100,000 people Affects men slightly more frequently than women Sporadic ALS is more common than familial ALS - accounts for up to 20% of cases Associated with degeneration of upper and lower motor neurons and in association with toxic protein accumulation # 02 Amyotrophic Lateral Sclerosis (ALS) - Pathogenesis - SODD1 gene - mutations in the gene encoding copper-zinc superoxide dismutase - Seen in chromosome 21 - accounts for about 20% of familial ALS - C9orf72 - Expansion of a hexanucleotide repeat in the 5'- untranslated region of a transcript of unknown function - accounts for about 40% of familial ALS - TDP-43 and FUS - encode stress granule proteins with RNA-binding capacity # 02 Amyotrophic Lateral Sclerosis (ALS) A type of motor neurone disease - ALS is a rare neurological condition - Progressive -- worsens with time -- with no cure - Gradually muscles under voluntary control are affected, individuals lose strength, ability to speak, eat, move, breath - Most people with ALS die of respiratory failure within 3 to 5 years of first symptoms - Affects nerve cells responsible for controlling voluntary muscle movement - Motor neurons link between brain and voluntary muscles - In ALS, the upper motor neurons and lower motor neurons degenerate and die - Unable to function, the muscles degenerate # 02 Vitamin Deficiencies - Thiamine (Vitamin B1) Deficiency - Wernicke-Korsakoff syndrome - Classical neurologic disease resulting from thiamine deficiency - Common in the setting of chronic alcoholism, but it may also be encountered in individuals with thiamine deficiency - Two related manifestations - Wernicke encephalopathy - characterized by acute psychosis and ophthalmoplegia - paralysis or eye muscles - symptoms are reversible when treated with thiamine - Korsakoff syndrome - Marked by disturbances of short-term memory and confabulation, making up stories to fill in the gaps - Vitamin B12 Deficiency - Causes Subacute combined degeneration of the spinal cord - Lesions result from a defect in myelin formation - Symptoms - Initially with bilaterally symmetrical numbness - Tingling - Slight ataxia in the lower extremities - Microscopic examination - Swelling of myelin layers, producing vacuoles in the affected tracts # 02 Neurologic Sequelae of Metabolic Disturbances - Hypoglycemia - Brain requires glucose and oxygen for its energy production - Cellular effects of diminished glucose resemble those of oxygen deprivation - Leads to selective injury to large cortical pyramidal neurons - May caused widespread injury to many areas of the brain - Hyperglycemia - most commonly associated with inadequately controlled diabetes mellitus - associated with either ketoacidosis or hyperosmolar coma - does not elicit significant morphologic changes in the brain - Patients becomes dehydrated and develops confusion, stupor, and eventually coma - Hepatic Encephalopathy - found in the setting of impaired liver function - mediators include elevated ammonia levels as well as proinflammatory cytokines - Alzheimer type II cells can also be seen - astrocytes with enlarged nuclei and minimal cytoplasm - Carbon Monoxide - Acute carbon monoxide exposure are the result of impaired oxygen carrying capacity of hemoglobin - Interacts with the heme of cytochrome C oxidase - Inhibiting tissue utilization of oxygen by blocking electron transport in the mitochondria - Selective injury of the neurons in: - Layers III and V of the cerebral cortex - Sommer sector of the hippocampus - Purkinje cells - Ethanol - Effects of acute ethanol intoxication are reversible - Chronic alcohol abuse is associated with a variety of neurologic sequelae, including Wernicke-Korsakoff syndrome from thiamine deficiency - Cerebellar dysfunction - 1% of chronic alcoholics - associated with a clinical syndrome of truncal ataxia, unsteady gait, and nystagmus. - Bergmann gliosis - Loss of Purkinie cells and proliferation of the adjacent astrocytes - Between the depleted granular cell layer and the molecular layer of the cerebellum - Radiation - Exposure of the brain to radiation can occur accidentally or as part of therapeutic regimens for tumors - High doses of radiation (>10 Gy) can cause: - Intractable nausea - Confusion - Convulsions - Rapid onset of coma followed by death - Pathologic findings consist of large areas of coagulative necrosis of white matter with all tissue elements within the area affected - Radiation can also induce tumor - Develop years after radiation therapy - Sarcomas, Gliomas, Leukemia and Meningiomas # 02 Diseases of the Central Nervous System ## Disease of the CNS - Cerebral Edema, Hydrocephalus, Raised Intracranial Pressure & Herniation - Annuai incidence: - 10 to 17 per 100,000 persons for intracranial tumors - 1 to 2 per 100,000 persons for intraspinal tumors - World Health Organization (WHO) classification - Segregates tumors into one of four grades according to their biologic behavior - Ranges from Grade 1 to Grade IV - Toxic and Acquired Metabolic Disease - e Disease - Tumors # 02 Gliomas Most common group of primary brain tumors Arise from the Glial Cells This includes: - Astrocytomas - Oligodendrogliomas - Ependymomas Tumor types have characteristic histologic features that form the basis for the classification: Derived from a multipotent progenitor cell that preferentially differentiates down a particular cellular lineage # 02 Gliomas - Astrocytoma - Brain tumor that arises from astrocytes - Classified based on their grade: - indicates how fast the tumor is growing and how aggressive it is - Grade I (Pilocytic Astrocytoma) - Slow-growing tumor - found in children and young aduits - least aggressive form of astrocytoma - often be cured by surgery - Grade II (Diffuse Astrocytoma) - Slow-growing tumor - found adults - may not be possible to completely remove this tumor by surgery - can sometimes progress to a higher grade over time - Grade III (Anaplastic Astrocytoma) - faster-growing tumor - more aggressive than grade II astrocytoma - require more aggressive treatment, such as radiation therapy and chemotherapy - Grade IV (Glioblastoma Multiforme) - most aggressive form of astrocytoma - most common malignant brain tumor in adults - grows quickly and can spread rapidly throughout the brain - treatment typically involves surgery, radiation therapy, and chemotherapy - prognosis is generally poor - Oligodendroglioma - Other major subtype of infiltrating glioma is comprised of cells that resemble oligodendrocyte - Has the best prognosis among glial tumors - 5% to 15% of gliomas - Most common in the fourth and fifth decades - Molecularly defined by an IDH mutation in combination with whole-arm chromosomal codeletion of 1p and 19q - Gross Findings - Gelatinous, gray masses - Often with cysts, focal hemorrhage, and calcification - Microscopic Findings - "Fried Egg" appearance - Sheets of regular cells with spherical nuclei containing finely granular chromatin - Surrounded by a clear halo of vacuolated cytoplasm - Ependymoma - Tumors that most often arise in proximity to the ependyma-lined ventricular system - NF2 gene on chromosome 22 is commonly mutated - Spinal cord is the most common location in adults - more frequent in the setting of neurofibromatosis type 2 (NF2) - Posterior fossa ependymomas often manifest with non-communicating hydrocephalus due to obstruction of the fourth ventricle - True Ependymal Rosette - Central lumen that is empty - Pervivascular Pseudorosette - Cell processes radiate around a central vessel # 02 Choroid Plexus Tumors - Both Benign and Malignant tumors are all rare tumors - Choroid plexus papillomas - Intraventricular tumors that are most common in children - Tends to occur in the lateral ventricle - Papillary growths recapitulate the structure of the normal choroid plexus - epithelioid tumor cells cover fibrovascular stalks - usually present with hydrocephalus due to obstruction of the ventricular system - Choroid plexus carcinomas - Resemble adenocarcinoma - Almost always found in young children - Gross Findings - solid, infiltrative tumors frequently with foci of hemorrhage and necrosis - Microscopic Finding - Show papillary architecture in better differentiated foci - Solid and composed of highly atypical cells arranged in sheets on poorly-differentiated areas # 02 Primary CNS Lymphoma (PCNSL) - 2% of extranodal lymphomas and 1% of intracranial tumors - Most common CNS neoplasm in immunosuppressed individual (AIDS and immunosuppression after transplantation) - Secondary CNS involvement usually affects the meninges or the CSF not the parenchyma that is seen in Primary CNS Lymphoma - Majority of primary CNS tumors are diffuse large B-cell lymphomas - Immunosuppressed patients - Malignant B cells are usually latently infected by Epstein-Barr virus (EBV) - Immunocompetent patients - Amplification and overexpression of the PDL1 gene - encodes an important immune checkpoint protein that inhibits T-cell responses # 02 Primary CNS Lymphoma - Perivascular growth of large atypical lymphoid cells - Diffuse and sheet-like distribution with continued proliferation - Apoptosis and necrosis are prominent - especially if the patient received steroids before biopsy. - Angiocentric growth of lymphoid cells is often accompanied by perivascular reticulin deposits in a concentric fashion # 02 Meningiomas - Predominantly benign tumors of adults - Arise from the meningothelial cells of the arachnoid and are usually attached to the dura - Can be found in the ventricular system - arise from the stromal arachnoid cells of the choroid plexus - Uncommon in children - Moderate female predominance (3:2) - Loss of chromosome 22q12 - Harbors the NF2 gene - Common lesion in the setting of Neurofibromatosis Type 2 (NF2) - Meningiomas without NF2 mutations - TRAF7, KLF4, AKT1 and SMO - Mostly involve the skull base and have a lower risk of malignant progression # 02 Meningiomas - Slow-growing tumors - Signs and Symptoms - Vague non-localizing symptoms - Focal findings referable to compression of underlying brain - Gross Finding - Firm, Lobulated mass with broad-based attachment to the dura mater # 02 Meningiomas - Meningothalial - Fibrous - Transitional - Psammomatous - Secrotory - Anglomatous - Microcystic - Lymphoplasmacyto-Rich - Motaplastic - Atypical - Clear Cell - Chordold - Anaplastic - Papillary - Rhabdoid # 02 Meningiomas: Meningothelial or Syncytial (WHO Grade 1) - Meningothelial - Fibrous - Transitional - Psammomalous - Secrotory - Anglomatous - Microcystic - Lymphoplasmacyte-Rich - Metaplastic - Lobules of cells with ample cytoplasm and indistinct borders (syncytial pattern) # 02 Meningiomas: Psammomatous Meningioma (WHO Grade 1) - Meningothelial - Fibrous - Transitional - Psammomatous - Secretory - Anglomatous - Microcysuc - Lymphoplasmacyto-Rich - Metaplastic - Concentric calcifications # 02 Meningiomas: Anaplastic Meningioma (WHO Grade III) - Criteria for Diagnosis: - Greater than or equal to 20 mitoses per 10 HPF - Frank anaplasia (sarcoma, carcinoma or melanoma-like histology) - Marked cellular and Nuclear pleomorphism # 02 Metastatic Tumors - Mostly carcinoma - Account for approximately one-fourth to one-half of intracranial tumors - Five most common primary sites (accounts to 80% of all metastases combined): - Lung - Breast - Skin (Melanoma) - Kidney - Gastrointestinal tract - Meningeal carcinomatosis - Disseminated subarachnoid, meningitis-like pattern of metastatic tumor cells in the meninges - Highly challenging to treat - Associated with both cranial and spinal neuropathies # 02 Familial Tumor Syndromes - Neurofibromatoses 1 (NF1) - Neurofibromatosis (NF1 and NF2) are familial autosomal dominant syndromes - Characterized by tumors of the peripheral and central nervous systems - NF1 is most common, with a frequency of 1 in 3000 - Characterized by: - Neurofibromas of peripheral nerves - Gliomas of the optic nerve - Pigmented nodules of the iris (Lisch nodules) - Cutaneous hyperpigmented macules (café au lait spots) - Neurofibromatoses 2 (NF2) - Frequency of 1 in 40,000 to 50,000 - Characterized by: - The occurrence of bilateral vestibular (cranial nerve VIII) schwannomas - Multiple meningiomas - Ependymomas of the cervical spinal cord - Schwannomatosis - Multiple non-vestibular schwannomas, either throughout the body or limited to one region - Involves the peripheral nervous system only - Roughly as common as NF2 - Individuals with schwannomatosis typically do not have vestibular schwannomas - tumors that arise from the vestibular nerve in the inner ear. - Tuberous sclerosis complex (TSC) - Autosomal dominant syndrome - Occurs at a frequency of approximately 1 in 6000 births - Development of hamartomas and benign neoplasms involving the brain and other tissues - Hamartomas in the CNS take the form of cortical tubers and subependymal nodules - Most frequent clinical manifestations includes: seizures, autism, and intellectual disability - TSC1 gene - Seen chromosome 9q34 - Encodes a protein called hamartin - TSC2 gene - Seen chromosome 16p13.3 - Encodes a protein called tuberin - Von Hippel-Lindau Disease - Autosomal dominant disease - Develop hemangioblastomas of the CNS - Hemangioblastomas are most common in the cerebellum and retina - Disease frequency is 1 in 30,000 to 40,000 - VHL gene - tumor-suppressor gene located on chromosome 3p25.3 - encodes HIF1 - Von is highest. # 03 Review Questions A 74-year-old woman sustains blunt head trauma in a motor vehicle accident. On admission to the hospital, she is conscious but disoriented. CT scan of the head shows a right temporal bone fracture and mild cerebral edema. Two days later, laboratory studies show serum Na+ - 109 mmol/L; K+ - 3.9 mmol/L; CI – 82 mmol/L. The hyponatremia is corrected over the next 2 hours with intravenous fluid and electrolyte therapy and diuretics. She then rapidly becomes confused and exhibits limb weakness. No papilledema is seen on funduscopic examination. What complication has most likely occurred in this woman? - Central pontine myelinolysis - Cerebellar tonsillar herniation - Cerebral edema sufficient to produce herniation would cause papilledema, not noted in this case - Intraventricular hemorrhage - Does not result from electrolyte and fluid disturbances - Wernicke-Korsakoff syndrome - Seen chronic alcoholism that affects mammillary bodies and periaqueductal gray matter # 04 Please read on the following topics - Acute Disseminated Encephalomyelitis and Acute Necrotizing Hemorrhagic Encephalomyelitis - Frontotemporal Lobar Degenerations (FTLDs) - FTLD-tau - FTLD-TDP - Atypical Parkinsonian Syndromes - Progressive Supranuclear Palsy (PSP) - Corticobasal Degeneration (CBD) - Multiple System Atrophy (MSA) - Spinocerebellar Degenerations - Spinocerebellar Ataxias (SCA) - Friedreich Ataxia Ataxia-Telangiectasia - Other Motor Neuron Diseases - Spínal and Bulbar Muscular Atrophy (Kennedy Disease) - Spinal Muscular Atrophy (SMA) - Tumors - Embryonal Neoplasms - Medulloblastoma - Paraneoplastic Syndromes