Cheat Sheet Brain Lobes

Cheat Sheet Patho1: Brain Lobes: 1. Frontal lobeè - Motor - Broca’s area in left frontal lobe (brain asymmetry plays a role here) , controls motor pattern of speech, if damaged è expressive dysphasia è associated with Wernicke’s area in the temporal lobe. - Personality, behavior, voluntary motor function, intellectual functions, problem solving, judgement; good bad/ right wrong. 2. Parietal lobe è - high order sensory areas - contains area for naming objects - contains area from processing of visual languageè reading 3. Occipital lobe è Visual cortex, works with other lobes, back/ rear of the brain. 4. Temporal lobe è - Sensory input - Wernicke’s area: auditory, visual & somatic associations combine in this area, if damaged è inability to understand spoken or written language (receptive dysphasia). Brain is asymmetric: - Left brain: logic, math skills, analytical & RIGHT side of body control. - Right brain: Creativity, emotion, face recognition, art & LEFT side of body control. Statistics of CNS: - 100 billion neurons Neurons: functional unit of CNS, receive & transmit info, can’t divide. - 10-50 x 100 glial cells (much more than neurons) - 40% of our genes participate in the formation of the CNS. Neural progenitors è - capable of dividing a limited number of times and have the capacity to differentiate into a restricted number of neuronal and glial cell types. - Zika virus infection during pregnancy is a cause of congenital brain abnormalities including microcephaly. it is thought that the virus does so by infecting progenitor cells (decreasing brain growth) . Glial Cells: 1. Astrocytesè - Gives structural support to neurons - Control neural biochemical environment. - It’s processes are associated with blood vessels è BBB - Most abundant CNS neuroglia - Participate in the transmission of messages & cell metabolism. 2. Oligodendrocytes è - Produce the myelin sheath; faster transmission of action potential by salutatory conduction. 3. Microglial cells è - Resident Macrophages - Mesoderm-derived phagocytic - Immune cells: clean injured brain areas from cell debris & eat the microbes that enter into the CNS. 4. Ependymal cellsè - Line the ventricle & spinal cord. - Forms choroid plexus that secretes CSF Reaction of Neurons to Acute injury: - Forms red neurons. a. Causes: hypoxia or ischemia b. Earliest morphologic manifestation of neuronal cell death c. Appear after 12-24 hrs of irreversible injury. d. Microscopically: shrinkage of cell body, pyknosis (apoptosis of nucleus), disappearance of the nucleolus and loss of Nissle substance (large granular substance made of RER with free ribosomes and found in neurons èThey are the site of protein synthesis) e. Loss of Nissl substance results in è intense cytoplasmic eosinophilia. ** Glial cells are less vulnerable to acute injury. Subacute and chronic neuronal injury: - = Degeneration - Neuronal death due to PROGRESSIVE disease - i.e Alzheimer - Cell loss affecting functionally related neurons (not necessarily structurally related). - Neuronal death is usually apoptotic and associated with reactive gliosis. ** chronic neuronal injury usually affects functionally related neurons Gliosis: - = increased glial cells (similar to fibrosis in the rest of the body) - Nonspecific reactive change of glial cells in response to damage in CNS. - Involves proliferation/ hypertrophy of several different types of glial cellsè astrocytes, microglia, oligodendrocytes. - Glial cells CAN PROLIFERATE AND DIVIDE in response to injury. Astrocytes during injury: - Principle cells responsible for repair and scar formation è gliosis - Reactive astrocytes during repair (to ANY form of injury) undergo changes è gemistocytic astrocyte (swollen cells) that include è 1. Hypertrophy and hyperplasia 2. Enlarged nuclei 3. Prominent nucleoli 4. Increased pink cytoplasm 5. Increased ramifying processes Microglia during injury: 1. Proliferating 2. Developing elongated nuclei è rod cells 3. Forming aggregates around small foci of tissue necrosis è microglial nodules/ granulomas. . 4. Congregating around cell bodies of dying neurons è neuronophagia. ** blood derived macrophages may also be present in inflammatory foci. Cheat Sheet Patho2: - PNS includes: spinal roots, spinal nerves and their branches, ganglia, and the cranial nerves 3-12. PNS è limited patterns of response to injury stimuli: 1. Axonal degeneration è axons become necrotic Reflects injury to axons but might involve neuronal cell bodies. If only distal axons are affected è regeneration is possible/ starts a week after injury. Types: a. Distal axonal degeneration: distal neuropathy only (cell body is spared). If the underlying cause is removed è regeneration and restoration of nerve function occurs. (MOST COMMON) b. Neurnopathies: cell body is damaged. Recovery is impossible. • Neuropathy: pathy in a nerve. Neuronopathy: cell body of the neuron is affected. • Neuropathy can be: Distal (peripheral) è affecting the axon or myelin. Proximal (Neuronopathy)è affecting the cell body. c. Wallerian degeneration: Occurs after trauma to a nerve. Important for repair. Type of axonal degeneration. 2. Segmental demyelination è Myelin sheath is degraded, axon is normal. a. Due to Schwann cell dysfunction. Schwann cells dysfunction could be: Primary: Injury related to Schwann cells or Myelin sheath Secondary: demyelination due to underlying axonal abnormality. b. Re-myelination occurs via proliferation of Schwann cells and function CAN BE RERSTORED (depending on the extent of damage). c. Repetitive cycles of demyelination/ re-myelinations è will results in increased number of Schwann cells encircling the axon èenlarged/ thickened nerve (hypertrophic neuropathy “clinically”) èONION BULB appearance “microscopically”. OCCURS IN CHRONIC demyelinating diseases! ** Axonal injury can cause secondary demyelination but not vice versa. 3. Both patterns è coexist but one might be predominate. PNS neuropathies: - Divided into: a. Axonal neuropathy o Most common: because neurons are more susceptible to injury than Schwann cells. o Conduction velocity near normal. o Causes (not for memorizing): ü Any disease that affects the blood supply/ischemia è axon damage. è i.e DM, Wegner’s granulomatosis, necrotizing vasculitis or infectious vasculitis. Polyarteritis nodosa and SLE. ü Cancer can damage the nerve. ü Trauma ü Certain toxins & nutritional deficiencies. & certain drugs. b. Demyelinating neuropathy: o Decreased conduction velocity. o Cause: hereditary or immunologic. o Can be acute or chronic. o Guillian Barre syndrome è causes ACUTE demyelinating neuropathy. - 80-90% of neuropathies are axonal. 1. Clinical features: - Symptoms related to impaired function of the damaged nerve: a. Muscle weakness and atrophy b. Sensory loss c. Pain d. Paresthesia: abnormal sensation of numbness, tingling, burning sensation with NO physical explanation of the sensation. e. Autonomic dysfunction è including loss of bowel and bladder control. 2. Causes: - Hereditary causes or immune destruction of myelin. - ANY disease process that affects the nerves or their blood supply can cause axonal neuropathy. - MOST COMMON CAUSE of generalized peripheral neuropathy è DIABETIC NEUROPATHY: a. Polyneuropathy or mononeuropathy b. Several forms of neuropathy: 1. Distal symmetric sensorimotor polyneuropathy (MOST COMMON FORM) 2. Autonomic neuropathy: causing changes In bowel, bladder, or cardiac function. 3. Lumbosacral neuropathy: causing pain in lower legs. c. Diabetic neuropathy mechanism is UNKNOWN (might be due to nerve ischemia because of small vessel disease) - Other causes of peripheral neyropathy è hereditary, alcoholism, chronic renal failure, neurotoxic drugs, autoimmune diseases, nutritional deficiencies, vasculitis, infections, tumours, trauma and amyloidosis. So : any toxins , infections, or infiltrative disease process or vascular disease can affect the nerve and cause neuropathy. Guillian Barre Syndrome: 1. Autoimmune neuropathy. 2. ACUTE! 3. Often follows bacterial viral or mycoplasma infection. 4. Can follow immunization or surgery 5. MOST COMMONLY after Campylobacter jejuni, CMV, EBV 6. CSF: INCREASED proteins and FEW WBC. 7. Has 2 forms: a. Demyelinating è predominant form in USA & Europe. b. Immune mediated axonal neuropathy è common in Asia. - Clinical Features: 1. Acute symmetric neuromuscular paralysis è often begins distally and ascends proximally. 2. Sensory and autonomic disturbances may occur 3. 5% of patients present with opthalmoplegia (paralysis of eye muscles), ataxia, and areflexia (absence of reflexes). If these symptoms exist, it’s called è Fisher Syndrome. 4. Muscle paralysis may cause RESPIRATORY DIFFICULTY è might lead to death! 5. Autonomic involvement may cause cardiac arrhythmia, hypo/hypertension. 6. RESOLVES 2-4 weeks after the onset and most patients recover. Chronic Inflammatory demyelinating Polyneuropathy CIDP: - Symmetric - Mixed sensorimotor polyneuropathy - Persists for 2 months or more - Immune mediated but usually not preceded by infection. - Occurs in patients with other autoimmune diseases and in HIV/AIDS patients. Cheat Sheet Patho3: Nerve Injury - Nerves of PNS can regenerate, but restoration of function is only possible if the injury is minimal. Repair can be improved by surgical intervention. Peripheral nerves can regenerate after trauma. - Axons of the CNS have a very LIMITED capacity to regenerate. Axons of PNS CAN regenerate è due to the difference response of oligodendrocytes and Schwann cells to injury. Explanation to the point above è 1. Oligodendrocytes respond to neural injury by apoptosis or entering a quiescent state and they have a very little phagocytic activity. SO clearance of degenerate debris is ineffective in CNS. 2. Astrocytes are activated during injury causing gliosis and produces inhibitory cytokines. This decreases the ability of axons to regenerate. - PNS axons have a capacity to regrow, but the functional recovery of nerve function depends on the extent of injury and can be improved by surgical approximation of injured nerve or by nerve grafts. - Nerve graft è surgical technique where a segment of an unaffected nerve is used to replace or bridge an injured nerve. è the donor nerve is usually a sensory nerve, where if a section is taken from it, some numbness will occur, but there will be no serious effects. i.e Sural nerve. Regeneration Steps: • Note: Debris happening due to the damage must be cleared. • Most important cells for phagocytosis hereè Schwann cells and macrophages 1. Injury to a nerve è inflammatory response of non-neuronal cells (Schwann & Microphages) 2. These cells cause degeneration (Wallerian denegation) of the distal parts to the injury. (1st step). This degeneration: a. clears the inhibitory debris in the “distal segment” of a peripheral nerve fiber. b. Aid in the production of an environment that supports axon regrowth. 3. Regeneration è Regrowth of the axon will take place down the endneural tube (rate 1-2 mm/day). Function of Schwann cells during regeneration: - Soon after injury è Schwann cells start to dedifferentiateè alter gene expression è so they can stop producing myelin & up regulate regeneration associated genes. - Divide/ Hyperplasia - Phagocytic activity è They remove myelin debris (which is barrier to growth of the axon. - Secrete neurotrophic factors, mainly cytokines è help in growth. - Recruit macrophages è also remove the debris - They can survive and support the nerve for 8 weeks. After 8 weeks, their function deteriorates and they die by apoptosis. è LIMITING successful long distance regeneration. - Nerves regenerate at a rate of 1-2mm per day. Traumatic neuroma: - If ends of a cut nerve are not approximated è the regenerating axons might grow haphazardly è forming a mass called è TRAUMATIC NEUROMA. - Traumatic neuroma: non-neoplastic mass related to previous trauma and composed of a haphazard mixture of axons, Schwann cells and connective tissue. - They contain abnormal nerve bundles è so the mass is usually PAINFUL. Tumors of PNS: 1. Benign tumors è Schwannoma & neurofibroma 2. Malignant tumors è Malignant peripheral nerve sheath tumor/ MPNST. A. Schwannoma: 1. Benign 2. Can arise in soft tissue, internal organs, spinal roots/ cranial nerves. 3. MOST CRANIAL NERVE AFFETCED è vestibular portion of the 8th è can result in hearing loss. 4. Grossly è a. encapsulated/ well circumscribed and composed of proliferation of Schwann cells b. hugs the nerve but not actually arising from it. ** point a and b makes it easy for full surgical removal of the tumor. 5. Can be sporadic or familial. a. Familial: - 10% of schwannomas - associated with neurofibromatosis TYPE 2 - Usually MULTIPLE ( i.e meningiomas and ependymomas) - hallmark for NF2 è Presence of bilateral vestibular schwannoma. (not all patients with NF2 have bilateral schwannomas) - Patients DO NOT HAVE NEUROFUBROMAS. - Genetic mutation in NF2: • Caused by loss of function mutation in MERLIN gene/ chromosome 22. • Merlin: cytoskeletal protein that is a tumor suppressor gene by facilitating E cadherin (most important factor) in mediating contact inhibition. • Mutant merlin è contact inhibition is lost è tumor proliferates. B. Neurofibroma 1. 2. 3. 4. - Benign Nerve sheath tumor NOT ENCAPSULATED Composed of proliferating Schwann cells admixed with other cells including mast cells and fibroblasts. 5. Can be sporadic or familial (neurofibromatosis type 1 = NF1). a. NF1: Autosomal dominant - Mutation in Neurofibromin è Tumor suppressor gene/ chromosome 17. Negative regulator for RAS oncoprotein. Patients have multiple neurofibromas, malignant peripheral nerve sheath tumor, optic gliomas, and other glial tumors. è MULTIPLE NEUROFIBROMAS. Patients have learning disability, seizures, pigmented nodules in the iris and pigmented skin lesions è café-aw lait spots. C. MPNST 1. 2. 3. 4. Malignant tumor Schwann cells 50% occur in the setting of NF1 Histologically è Highly cellular, anaplastic, pleomorphic, and show necrosis and a high mitotic rate.