Pathologie (Fach) / Neurologie (Lektion)

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• Meningeom 1. Druckatrophie: Expansives Wachstum. Drückt auf Hirnsubstanz. 2. Wirbel: Spindelige, wirbelartig angeordnete Zellen. 3. Psammomkörperchen: Im Zentrum der WIrbel findet man nekrotische Zellen, die verkalken und dunkelblaue Kugeln bilden. 4. Isomorphes Zellbild 5. „Lochkerne“: helle, vakuolenartige Einschlüsse in den Kernen 7. Starke Vaskularisierung Morphologische Varianten: Klassisch, meningoendotheliomatös, fibromatös, angiomatös, sarkomatös.
• Meningitis 1. Entzündiliches Exudat in den Leptomeningen. 2. Aktive Hyperämie: Ausgeweitete Blutgefässe. 3. Fibrinausschwitzungen. 4. Keine Ausbreitung ins Hirnparenchym (Meningoenzephalitis). 5. Bakterien Kolonien.
• Multiple Sklerose Degenerationsherd 1. Entmarkungsherde: Im Bereich der weissen Substanz sind lokalisierte Herde mit geringerer Anfärbbarkeit. 2. Schwund der Markscheiden. 3. Diskrete zellige Reaktion: T-Lymphozyten und Makrophagen. 4. Glianarbe.
• Hirninfarkt (Stadien I-III) Stadium I: Akut1. Eosinophile Zellen mit pyknotischen Nuklei und nicht erkennbaren Nukleoli ("red neurons").2. Ödematöse Auflockerung des Hirnparenchyms. Stadium II: Subakut1. Kolliquationsnekrose (Neutrophile setzen lysosomale Enzyme frei)2. Makrophagen, "Fettkörnchenzellen"3. Einsprossende Gefässe4. Spongiöse Parenchymauflockerung Stadium III: Alt- Destruktion des Parenchyms mit Defektbildung- Glianarbe oder Pseudozyste
• Gliale Tumoren - Astrozytome1. Pilozystisches Astrozytom (WHO Grad I)2. Diffuses Astrozytom (WHO Grad II)3. Anaplastisches Astrozytom (WHO Grad III)4. Glioblastom (WHO Grad IV) - Oligodendrogliale Tumore1. Oligodendrogliom (WHO Grad II)2. Anaplastisches Oligodendrogliom (WHO Grad III) - Ependymome
• Glioblastoma multiforme Makroskopie: - Relativ umschriebene Tumoren trotz infiltrativen Wachstums- Charakteristische „bunte“ Schnittfläche Mikroskopie:1. Palisadenartige Aufreihung von Tumorzellen im Randbereich der Nekrosen2. Gefässproliferate: Neugebildete Blutgefässe, insbesondere Kapillaren3. Hämorrhagien4. Zellpolymorphie mit Mitosen, mehrkernige Zellen
• Ependymom (WHO Grad II) 1. Echte Rosetten: radiäre Anordnungen der Tumorzellen mit Ausbildung tubulärer Lumina 2. Pseudorosetten: Tumorzellen um zentral gelegene Gefässe 3. Keine Zeichen der Malignität (Mitosen, Anaplasiezeichen) Makroskopisch:- Grob- bis feinknotige, relativ scharf abgegrenzte Tumoren mit grauer Schnittfläche
• Oligodendrogliom (WHO Grad II) 1. Isomorph: Gleichmässiger Aufbau. 2. Spiegelei-Zellen: Uniforme runde Zellen und perinukleäre Halos. ("Honigwabenarchitektur") 3. Verzweigtes Gefässnetz (maschendrahtartig) ("chicken wire") 4. Verkalkungen. 5. Keine mitotische Aktivität. Makroskopisch:- Relativ gut abgegrenzte grau-rötliche Tumoren- Häufig Blutungen, Verkalkungen und Invasion des Subarachnoidalraums
• Kraniopharyngeom (WHO I) 1. Ektopisches Epithel: Ein- bis mehrschichtiges Plattenepithel aus Resten der Rathke-Tasche mit Zystenbildung. 2. Verhornungen („wet keratin“) und Verkalkungen mit Cholesterinkristallen. 3. Keine Malignitätszeichen.
• Schwannom (WHO Grad I) 1. Synzytiales Wachstumsmuster 2. a) Antoni-A-Formation: Zellreiche Areale mit spindelzelligen Tumorzellen mit lang gestreckten Zellkernen.b) Antoni-B-Formation: Zellarme Areale mit überwiegend lipidhaltigen Tumorzellen. 3. Verocay Bodies: Innerhalb der Antoni-A-Formation liegend palisadenartige Aufreihung der Tumorzellkerne  Immunhistologisch: Nachweis von S100-Protein.Bilaterale Schwannome des N. VIII sind die Hauptmanifestation der NF Typ II.
• Medulloblastom (WHO Grad IV) 1. Sehr zelldichter, klein-, rund- und blauzelliger Tumor. 2. Hämorrhagien 3. Viele Apoptosen, erhöhte mitotische Aktivität. 4. Homer-Wright rosettes
• Arteriovenöse Malformation 1. Grosslumige Gefässanschnitte 2. Wandkaliberschwankungen: extreme Ausdünnung oder Verdickungen der Gefässwand 3. Gliotisch verändertes, teilweise frisch eingeblutetes Hirngewebe
• Kavernom - Dicht aneinanderliegende Gefässanschnitte ohne regelrechten Wandaufbau - Stark ausgedünnte Gefässwände (vgl. AV-Malformation wo verdünnt und verdickt) - Hämosiderinablagerungen als Zeichen früherer Einblutungen
• Leptomeningeal carcinomatosis Häufigste Krebsarten: - Brustkarzinom - Lungenkarzinom - Melanom
• Pediatric brain tumors Infratentorial tumor:- Juvenile pilocytic astrocytoma→ Most common primary pediatric tumor→ Mostly in the cerebellum near the brainstem→ Grade I→ Cysts, bodies of granular material, Rosenthal fibers, contain glial fibrillary acidic protein- Medulloblastoma→ Most common malignant tumor→ Originate form embryonic stem cells→ Tend to be extremely aggressive→ Metastasize through cerebrospinal fluid (drop metastasis)→ Grade IV→ Homer-Wright rosettes- Ependymoma→ Form in the IV ventricle→ Graded I-III→ Perivascular pseudorosettes (tumor cells surrounding centralized blood vessel) Supratentorial:- Craniopharyngeoma→ Most common supratentorial tumor→ Remnants of Rathke's pouch→ Grade I→ Cysts filled with oily fluid, cells that stratify, "wet keratin"- Pinealoma→ Primarily emerge from endocrine cells of the pineal gland→ Grade I-IV- Round tumor cells resembling germline→ Homer-Wright rosette Symptoms:- Headaches, nausea, vomiting, seizures- Pinealoma may lead to ↑ secretion of β-HCG → early onset puberty- Pinealomas, medulloblastomas and ependymomas can cause hydrocephalus Diagnosis:- CT, MRI- Biopsy Treatment: Surgical removal, radiotherapy, chemotherapy guided by molecular characteristics
• Craniopharyngeoma Benign tumor arising from a remnant of the Rathke pouch (ectodermal derivative). Bimodal distribution: 5–14 years; second peak at 50–75 years. Symptoms:- Compression of the optic chiasm → bitemporal hemianopsia- Compression of the infundibular stalk → disconnection hyperprolactinemia- Compression of the pituitary gland due to intrasellar extension → hypopituitarism Diagnostics:- Imaging: Suprasellar calcified cyst with a lobulated contour- Biopsy:→ Cholesterol crystals found in a motor oil-like fluid on gross examination→ Histological variants:1. Adamantinomatous (common):- Reticular epithelial cells- Frequently associated with calcifications- Cysts and keratin nodules2. Papillary- Metaplastic squamous cells- Calcifications and cysts are rare- No keratin nodules Treatment: Resection + adjuvant radiotherapy
• Ependymoma Benign tumor that arises from ependymal cells of the ventricular system. Peak incidence: children and young adults Clinical features:- The 4th ventricle is the most common location in children → non-communicating hydrocephalus → features of raised intracranial pressure (eg, papilledema, headache) Diagnostics:- Imaging: Intra-parenchymal tumor with calcifications and cystic components due to necrosis and/or hemorrhage- Biopsy:→ Perivascular pseudorosettes→ Rod-shaped bodies (blepharoblasts) near the nucleus Treatment: Resection + adjuvant radiotherapy
• Medulloblastoma Highly malignant tumor derived from primitive, neuroectodermal tissue.- Most common malignant pediatric brain tumor (approx. 20-25% of all cases) Peak incidence: 1st decade Associated conditions: Turcot syndrome- Wnt (15%)- SHH (25%)- Non-Wnt/SHH (60%) → bad prognosis Clinical features:- The most common location is the cerebellum → cerebellar defects (eg, broad-based gait)- Most tumors arise within the cerebellar vermis (midline)- Invasion or compression of the 4th ventricle → non-communicating hydrocephalus → features of raised intracranial pressure (eg, papilledema, vomiting, headache)- Drop metastases are common → paraplegia Diagnostics:- Imaging: Intraparenchymal contrast-enhancing mass- Biopsy: anaplastic small round blue cells that surround a central neuropil (Homer-Wright rosettes) Treatment: Resection + adjuvant therapy- Children ≥ 3 years: chemotherapy and craniospinal radiotherapy- Children < 3 years: chemotherapy
• Oligodendroglioma Tumor that arises from oligodendrocytes.- LOH 1p und 19q - Median age: 40–50 years Clinical features:- The most common location is the cerebral hemisphere (typically the frontal lobe) → seizures, focal neurological deficits, personality changes Diagnostics:- Imaging: Intra-parenchymal tumor with calcifications- Biopsy: → Cells with a clear cytoplasm and round nucleus (fried egg cells) → Chicken-wire pattern of capillary anastomoses Treatment: Resection + adjuvant radiotherapy and chemotherapy
• Glioblastoma Most common primary nervous system cancer- 65-75 years of age- O(6)-methylguanine-DNA methyltransferase (MGMT) gene encodes DNA repair enzyme that abrogates the effects of alkylating chemotherapy→ Epigenetic silencing MGMT gene by promoter methylation predicts response to alkylating agents Location: White matter of the cerebral hemisphere (possibly bilateral = butterfly glioma) Clinical features:- General clinical features of brain tumors (eg, epileptic seizure)- Apoplectic glioma: mimics an intracranial hemorrhage; symptoms of raised ICP Diagnostics:- Imaging- Biopsy: → Diffuse infiltration of the central nervous system tissue → “Pseudopalisading” pleomorphic tumor cells surrounding areas of necrosis → Multiple mitotic figures→ Hemorrhage→ Microvascular proliferation Treatment: - Surgical resection- Palliative percutaneous radiotherapy/chemotherapy (temozolomide)- Glucocorticoids (in intracranial pressure)
• Adult brain tumors Supratentorial:- Glioblastoma (Grade IV)→ Mostly in cerebral hemispheres and rapidly cross the corpus callosum→ Angiogenesis, but nutrient demand outpaces blood supply → viable cells line up around necrosis in the middle (pseudo-palisading pattern)- Meningeoma→ From arachnoid cap cells→ Form in parasagittal regions and on the surface of the brain under the dura mater→ Graded I-III (relatively slow growing)→ Nests of cells (= multinuclear syncytium of fused cells)→ Psammoma bodies (calcifications)- Pituitary adenoma→ Formed by hormone secreting cells of the anterior pituitary- Oligodendroglioma (rare)→ Typically form in the frontal lobes, wher neurons are heavily myelinated→ Grade II-III (relatively slow growing, can be malignant)→ Round nuclei with halos ("fried egg" appearance)→ "Chicken wired" pattern of blood vessels with areas of calcification Infratentorial:- Hemangioblastoma→ Derived from cells with blood vessel origins→ Often found in the cerebellum→ Grade I (slow growing)→ Thin-walled capillaries that are closely arranged Symptoms: Headaches, nausea, vomiting, seizures Diagnosis: MRI, CT scans, tissue biopsy
• Meningioma Almost always benign, slow-growing brain tumors that arise from arachnoid cap cells of the arachnoid villi.- Most common primary brain tumor in adults- Sex: F > M (3:2) - Peak incidence: patients in their 60's- WHO I, II (atypical meningeomo, III (anaplastic meningeoma) Etiology:- Ionizing radiation: Radiotherapy for head and neck tumors, dental x-rays- Multiple meningiomas may develop in patients with type II neurofibromatosis. Pathology:Gross findings: - Encapsulated, round, grayish-white tumor- Firm to hard consistency- Cross-sectional surface: gray, granularMicroscopic findings:- Mesenchymal origin (arachnoid cap cells)- Onion peel arrangement of tumor cells- Psammoma bodies- Increased vascularity Therapy: Surgical resection + Radiotherapy
• Schwannoma Schwannomas are benign tumors that arise from Schwann cells and primarily originate within the vestibular portion of cranial nerve VIII. - Median age: 50 years- Most common tumor of the cerebellopontine angle- Unilateral in 90% of cases (bilateral in Neurofibromatosis type II) Symptoms:Early symptoms with insidious onset: caused by pressure on the vestibulocochlear nerve (CN VIII) as a result of tumor expansion into the internal acoustic canal (internal auditory meatus)- Cochlear nerve involvement: Unilateral sensorineural hearing loss (most common symptom), tinnitus- Vestibular nerve involvement: Dizziness, unsteady gait and disequilibrium Pathology:- Simultaneous occurence of areas with densely packed nuclei (palisade pattern) as well as scattered or anuclear areas - Antoni-A region: Cell extension bundles without nuclei alternate with a multitude of closely arranged glia cells- Antoni-B region: Tumor cells form a loose mesh with their appendices- Capsule
• Gehirnmetastasen - 15% der malignen Geschwülste im Hirn 1.- Häufigste bei Mann: Bronchialkarzinom- Häufigste bei der Frau: Mammakarzinom2. Melanom3. Nierenzellkarzinom Clinical features:- Headaches- Cognitive deficits- Focal neurological deficits- Seizures Diagnostics:- Neuroimaging findings: Well-circumscribed tumors at the junction of gray and white matter and/or watershed areas of the arterial system - Work-up if the primary tumor is unknown: Whole body contrast CT and/or PET scan→ If no primary tumor is found or if the tumor is not surgically accessible: biopsy of the brain metastasisGlucocorticoids to reduce tumor edema Therapie: - Solitärmetasatase: Operativ oder stereotaktische Radiochirurgie- Extensive brain metastases: stereotactic radiosurgery, whole brain radiation therapy, or chemotherapy- Hirnödem: Kortikosteroide und Antiepileptika Meningeosis neoplastica bezeichnet die Metastasierung von Tumorzellen in die weichen Hirnhäute. Sie kann bei vielen Tumoren auftreten und wird entsprechend benannt (zB M. carcinomatosa, M. gliomatosa, M. lymphomatosa). Nachgewiesen wird sie durch eine Liquorpunktion.
• Ischemic stroke - Histology <24 hours: Eosinophilc cytoplasm + pyknosic nuclei (red neurons) 24-72 hours: Necrosis + neutrophils 3-5 days: Macrophages (microglia) 1-2 weeks: Reactive gliosis (astrocytes) + vascular proliferation >2 weeks: Glial scar
• Arteriovenous malformation Abnormal, congenital arteriovenous connections between arteries and veins that lead to venous hypertension, ischemia, and/or hemorrhage. Etiology:- Congenital- Osler-Weber-Rendu syndrome- Belong to the RASopathies Vessels can tangle up and called nidus ("nest). When a single artery and vein link up, they form an arteriovenous fistula.High pressures can cause arteries to dilate form aneurysms, and veins to undergo fibrosis. Vessels are at risk of tearing. Most common: Brain, spinal cord, lungs Symptoms:- Brain: Microbleeds, subarachnoid hemorrhage → headaches, seizures, focal deficits- Spinal cord: Sensory disturbances, muscle weakness, paralysis- Lungs: Shortness of breath, hemoptysis- Blood shunts past capillaries → heart works harder → heart failure Diagnosis:- Angiography (gold standard)- CT scan/MRI- Bruit (sometimes patient can hear it) Treatment:- Surgical excision- Radiosurgery: Radiation scars vessels- Endovascular embolization: Catheter occludes vessel
• Meningitis (english) Etiology:- Otitis media, sinusitis- CSF leak after head trauma or neurosurgery- Crowded living conditions (e.g., college dormitories, military barracks) Pathogens:- Newborns: Group B Streptococcus (most common), Escherichia coli, Listeria monocytogenes- Children (6 months-6 years): Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae- Teens/Adults (6-60 years): Neisseria meningitidis (most common in teens), Streptococcus pneumoniae, Enteroviruses, Herpes simplex virus (HSV-2)- Elderly (>60 years): Streptococcus pneumoniae (most common), gram-negative bacilli, Listeria monocytogenes- Immunocompromised patients: Listeria monocytogenes, gram-negative bacilli, Streptococcus pneumoniae, Cryptococcus spp., CMV, VZV, HSV, JC virus, Mycobacterium tuberculosis, toxoplasma gondii Clinical presentation:- Classic triad of meningitis: fever, headache, and neck stiffness (nuchal rigidity)- Altered mental status- Photophobia- Nausea, vomiting- Malaise- Seizures- If due to N. meningitidis: myalgia and possibly petechial rash; Waterhouse-Friderichsen syndrome Diagnostics:- Signs of meningeal irritation: Kernig sign and Brudzinski sign- Papilledema (< 5% of cases)- Lab: Blood glucose to assess CSF glucose, ↑ WBC, coagulation studies- Lumbar puncture Treatment:1. Blood cultures2. Lumbar puncture3. Immediate empirical antibiotics<1 month: ampicillin plus cefotaxime or aminoglycoside (eg, gentamicin)>1 month to <50 years: vancomycin plus third-generation cephalosporin (eg, cefotaxime or ceftriaxone)>50 years: vancomycin plus ampicillin plus third-generation cephalosporin (eg, cefotaxime or ceftriaxone)
• Abszess 1. Grosser nekrotischer Herd mit umgebendem Granulationsgewebe. 2. Innerhalb der Nekrose sind viele septierte Pilzhyphen zu finden, welche sich spitzwinkelig, dichotom verzweigen (vereinbar mit Aspergillus). 3. Um das nekrotische Areal herum stellt sich die reaktive Astrozytose (Gliose) mit Gewebsauflockerungen und Makrophagen dar.
• Aspergillosis Pathogen: Aspergillus fumigatus , Aspergillus flavus- Transmission: airborne exposure to mold spores (ubiquitous) Risk factors:- Destructive pulmonary pathology → Scar tissue or lung cavities (eg, from tuberculosis), COPD, emphysema- Severe immunosuppression (eg, HIV, neutropenia) → invasive aspergillosis- Pre-existing bronchopulmonary conditions (eg, asthma or cystic fibrosis) → ABPA Clinical presentation:- ABPA: associated asthma or CF; causes bronchiectasis and eosinophilia- Pulmonary aspergilloma (especially after Tb infection): chronic cough, hemoptysis- Invasive aspergillosis: fever, cough, respiratory distress- Endocarditis Diagnosis:- ABPA: eosinophilia, ↑ IgE, pulmonary infiltrates on chest x-ray or CT- Pulmonary aspergilloma: x-ray or CTshows mobile fungus ball; serology is positive for Aspergillus IgG- Invasive aspergillosis: silver/PAS-stainingon tissue biopsy: 45° angle branching septate hyphae with fruiting bodies Treatment:- ABPA: oral prednisone if severe; itraconazole if recurrent- Pulmonary aspergilloma: lobectomy for massive hemoptysis- Invasive aspergillosis: IV voriconazole
• Cerebellum - Histology The cerebellar cortex is composed of 5 types of neuronal cells, densely packed and arranged in 3 layers.All cerebellar neurons, except for the granule cells, are GABAergic inhibitory neurons. 1. Stratum moleculare- Basket cells (Korbzellen): large axons with sparse dendrites- Stellate cells (Sternzellen): star-shaped neurons with multiple arborizations- Parallel fibers (axons of granule cells)- Contains numerous dendrites from Purkinje cells- Receives excitatory input from parallel fibers- Sends inhibitory impulses to Purkinje cells 2. Stratum purkinjense- Purkinje cells (brain)→ A single layer of flat neurons with fan-like dendritic projections→ Axons run perpendicular to the parallel fibers of the granule cells- Receive excitatory input from climbing fibers and granule cells- Send inhibitory impulses to the deep cerebellar nuclei and thereby control the output of all motor coordination of the cerebellum- Purkinje fibers are the only efferent pathway to the deep cerebellar nuclei. 3. Stratum granulare- Golgi cells: located in the upper portion of the granular layer→ Receive excitatory impulses from molecular layer and send inhibitory impulses to the granule cells- Granule cells→ Most abundant cell type in the brain→ Composed of small, densely packed neurons→ Receive excitatory input from mossy fibers and send excitatory efferents to the Purkinje cells
• Astrozytom 1. Mässig pleomorpher, diffus infiltrierender Tumor mit astrozytärer Differenzierung 2. Tumorzellen mit meist runden Zellkernen von feingranulärem Chromatin 3. Blass-eosinophile Zytoplasmaleiber mit feinen Zellfortsätzen, die eine feinfibrilläre Tumormatrix bilden 4. Mikrozysten
• Syndrome NF-1: Neurofibroma, optic nerve glioma NF-2: Schwannoma, ependymoma, meningeoma Tuberous sclerosis: Subependymal giant cell astrocytoma von Hippel Lindau: Hemangioblastoma
• Pilocytic astrocytoma - Children and young adults (< 20 years) Localization: Usually in the midline- Most common: posterior cranial fossa (infratentorial)→ Cerebellum- Less common: optic pathway (optic glioma), hypothalamus, cerebral hemispheres (supratentorial) Symptoms:- Vomiting, ataxia- Failure to thrive (impaired growth)- Often associated with neurofibromatosis type I - Well-demarcated cystic lesion often with a bright contrast-enhancing solid nodule in the wall of the cyst Macroscopic: Nodular, rough tumor with a gray-white surface, ocassionally cystsMicroscopic: Few cells, Rosenthal fibers (eosinophilic, corkscrew fibers) KIAA1549-BRAF fusion ~65% Treatment: Surgical resection
• Major neurocognitive disorder (Dementia) Acquired disorder of cognitive function that is commonly characterized by impairments in memory, speech, reasoning, intellectual function, and/or spatial-temporal awareness. Etiology:- Neurodegenerative brain diseases→ Alzheimer disease (>50% of dementia cases)→ Parkinson disease→ Frontotemporal dementia→ Dementia with Lewy bodies→ Progressive supranuclear palsy→ Huntington disease- Cerebrovascular disease (20% of dementia cases)→ Multi-infarct dementia→ Diffuse white matter disease (subcortical arteriosclerotic encephalopathy)- Hypoxic brain damage- Normal pressure hydrocephalus- After head trauma, intracranial bleeding or brain tumors- Drug/alcohol‑related (e.g., Wernicke‑Korsakoff syndrome)- Wilson disease- Vitamin deficiencies (thiamine, B6, B12, folate)- Metabolic: exsiccosis, uremia, electrolyte imbalances, hypo-/hyperthyroidism, hypo-/hyperparathyroidism- Inflammatory/infectious: Syphilis. progressive multifocal leukoencephalopathy, HIV, Creutzfeldt-Jakob disease Diagnostics:- Personal and collateral history of cognitive and behavioral changes- Drug history- Screening for depression- Physical and neurological examination- Cognitive assessment: MMSE, Clock-drawing test- Lab tests:→ In all patients: screening for vitamin B12 deficiency→ More specialized tests should be ordered in patients with a rapid progressive course of dementia, young patients (< 60years), or patients with symptoms giving reason to suspect the presence of a certain disease: Serum electrolytes, renal and liver function tests, folate, homocysteine, ceruloplasmin, ApoE genotyping→ Lumbar puncture and CSF analysis (only in selected patients)- Imaging:→ In all patients: noncontrast head CT or MRI: To detect reversible causes of dementia (e.g., brain tumor, subdural hematoma, NPH, past cerebral ischemia), multiple lacunar infarcts in vascular dementia, reduced hippocampal volume in Alzheimer disease→ PET, SPECT: To distinguish between different neurodegenerative disorders (e.g., Alzheimer disease, atypical parkinsonian disorders, and frontotemporal dementia)→ EEG: when structural abnormality is suspected
• Altersveränderungen Nerven: Lipofuszin Glia: Corpora amylacea Blutgefässe: Mineralisierungen Extrazelluläre Matrix: senile Plaques
• Vascular dementia Result of multiple arterial infarcts and/or chronic ischemia. Risk factors:- Advanced age- History of stroke- Conditions associated with cardiovascular disease: chronic hypertension, hyperglycemia, hypercholesterolemia/hypertriglyceridemia, obesity- Traumatic brain injury with intracranial or intracerebral hemorrhage Etiology:- Large artery occlusion (usually cortical ischemia)- Lacunar stroke (small vessel occlusion resulting in subcortical ischemia)- Chronic subcortical ischemia Clinical features:- Step-wise decline in cognitive ability with late-onset memory impairment.- Asymmetric or focal deficits (e.g., hemiparesis) Imaging: CT/MRI usually shows lacunar infarcts Pathology:- Degeneration of the white substance- Lacunar infarcts- Arterio- und arteriolosclerosis- Enlargement of the perivasal space
• Alzheimer disease Most common cause of dementia in elderly. - Down syndrome patients have ?risk of developing Alzheimer disease, as APP is located on chromosome 21.- ↓ ?ACh.- Associated with:ApoE-2: ↓ risk of sporadic formApoE-4:? ↑ risk of sporadic formAPP, presenilin-1, presenilin-2: familial forms (10%) with earlier onset Clinical features:- Slowly progressive, over ∼8-10 years- Episodic impairment of memory- Characteristic order of language impairment: naming → comprehension → fluency Diagnosis:- AD is a clinical diagnosis- Diffuse cortical atrophy- Hippocampal atrophy- CSF: ↓ Beta amyloid, ↑ Phosphorylated tau Pathology:- Neuritic plaques (amyloid beta peptides, mainly accumulating extracellularly)- Neurofibrillary tangles (abnormally phosphorylated tau protein, which accumulates intracellularly)
• Das Tau Protein Stabilisiert Mikrotubuli (Proteine des Zytoskelett) Es existieren sechs verschiedene Tau-Formen (alternatives Splicing) Verschiedene Formen sind mit verschiedenen Proteinopathien assoziiert- Progressive supranuclear palsy- Corticobasal degeneration- Pick's disease/Frontotemporal dementia
• α-Synuklein Presynaptisches Protein involviert im vesikulären Transport. Lewy bodies bestehen aus missgefaltetem α-Synuklein Aggregaten α-Synucleinopathie- Diffuse Lewy Body dementia- Parkinson disease- Multi system atrophy
• TDP-43 = Transactive response (TAR) binding protein - Nukleäres Protein - Ablagerungen bei frontotemporaler Demenz- Ablagerungen bei Amyotropher Lateral Sklerose
• Frontotemporal dementia (Pick's disease) FTD is a heterogeneous group of syndromes that involve degeneration of the frontal, insular, and/or temporal cortices and manifest with a number of symptoms of dementia.- Age of onset: usually 40-60 years (typically younger than Alzheimer's disease!) Clinical features:- Early changes in personality and behavior → failure to observe social etiquette→ Apathy, disinhibition (e.g., hypersexual behavior), exaggerated emotional display, irritability, binge eating (particularly of sweet foods)- Intelligence, orientation, and memory initially intact- Aphasia (but no apraxia)- May have associated movement disorders (eg, parkinsonism) Macroscopic:- Atrophy of the temporal and/or frontal lobesHistology:- Nonspecific gliosis; formation of microvacuoles and loss of neuronal tissue- Detection of different types of intracellular inclusions in surviving neurons (tau or TDP-43 in approx. 90% of cases)- Hyperphosphorylated tau proteins (3R isoforms) → form tangles = Pick bodies- Ubiquinated TDP‑43
• Lewy body dementia Second most common form of neurodegenerative dementia (10-20% of dementia cases). Pathology:- Cerebral atrophy, particularly of the frontal lobe with relative sparing of the hippocampi- Lewy bodies (α-synuclein-positive cytoplasmic inclusions) = Hyaline eosinophilic, dark inclusions that are found inside brain neurons. Clinical presentation: The sequence of symptoms is more variable than in most other types of dementia.- Extrapyramidal motor symptoms- Visual hallucinations and paranoid episodes- Fluctuating cognition/alertness- Frequent falls- Rapid eye movement sleep behavior disorder (RBD)- Increased sensitivity to neuroleptic medication Antipsychotics are contraindicated!
• CADASIL = Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy The most common heritable cause of stroke and vascular dementia in adults. - Autosomal dominant - Mutations in NOTCH 3 Clinical presentation:- Migraine with aura - Subcortical ischaemic events - Mood disturbances - Apathy  - Cognitive impairment
• Layers of the cerebral cortex Most of the brain is composed of six layers. These areas are referred to as the neocortex. The hippocampus and the olfactory cortex are only composed of three layers and together are referred to as the allocortex. In addition, the cerebral cortex is divided into 47 Brodmann areas. 1. Molecular layer 2. External granular layer 3. External pyramidal layer 4. Internal granular layer → termination area of thalamocortical projections (form lines of Gennari in the primary visual cortex) 5. Internal pyramidal layer → area where axons of the corticospinal and corticobulbar tracts form 6. Multiform layer → composed of polymorphic cells
• Virchow-Robin-Raum Ein mit Flüssigkeit ausgefüllter, perivaskulärer Spaltraum um die Blutgefässe des zentralen Nervensystems - mit Ausnahme der Kapillaren.
• Multiple sclerosis Chronic, degenerative disease of the CNS that is caused by an immune-mediated inflammatory process.- Sex: F > M (2:1)- Age of onset: 20-40 years of age- Ethnicity: ↑ prevalence among the white population- Prevalence is greater among people in temperate zones Most common sites of demyelination in MS1. Periventricular areas2. Brainstem3. Cerebellum4. Spinal cord Clinical features:- Optic neuritis (most often the earliest manifestation): impaired vision and color blindness- Internuclear ophthalmoplegia (INO) as a result of a lesion in the medial longitudinal fasciculus (MLF)- Demyelination of spinal cord tracts→ Lhermitte's sign: a shooting electric sensation that travels down the spine when the patient flexes his/her neck→ Pyramidal tract lesion: upper motor neuron weakness characterized by spasticity, hyperreflexia, and a positive Babinski's sign → Involvement of the dorsal spinal column: loss of vibration and fine touch sensations, numbness, paresthesias, sensory ataxia- Cerebellar involvement → Charcot's neurological triad:- Scanning speech- Nystagmus- Intention tremors- Cranial nerve palsies- Autonomic dysfunction: bowel and bladder disorders, impaired sexual activity- Change in mental state: memory deficits, impaired concentration, and/or depression- Uhthoff's phenomenon: a reversible exacerbation of neurological symptoms following physical exertion, a warm bath, or fever Stages:1. Relapsing-remitting (90%)2. Secondary progressive (arises from above)3. Primary progressive (10%) Diagnostics:- Plain MRI (brain and spine)- Electrophysiological studies- Lumbar puncture: Lymphocytic pleocytosis, oligoclonal bands Treatment:- Acute exacerbations: High-dose glucocorticoid therapy for 3-5 days (methylprednisolone 500–1000 mg/d IV or PO)- Disease-modifying MS therapy (prevention of exacerbations): Interferon-β, glatiramer acetate, fingolimod, alemtuzumab, natalizumab Differential diagnosis:- Neuromyelitis optica (Devic's disease)- Acute disseminated encephalomyelitis (ADEM, acute demyelinating encephalomyelitis)
• Cerebral edema Excess accumulation of fluid within the brain parenchyma as a result of damage to the blood-brain barrier and/or the blood-CSF barrier. Etiology:- Cerebral infarction (stroke)- Iatrogenic (Rapid lowering of glucose or rapid correction of hypernatremia)- Trauma (particularly in closed head injury)- Toxic (e.g., lead intoxication)- Inflammatory (e.g., meningitis)- Space-occupying lesions (e.g., brain tumors, intracranial hemorrhage) Management: treatment of raised ICP

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