CNS third year med students Summary of midterm material H Awad

Transcription

1 CNS third year med students 2018 Summary of midterm material H Awad

2 Dear All This presentation summaries the main important topics covered in the midterm material ( lectures 1-6) There will be two questions from this summary in the final exam. I will send the details of the final exam later. Good luck.

3 CNS cells and their functions CNS cells are of two types: neurones that are the functional units and glial cells which are supportive. glial cells are much more abundant. Glial are four types: 1.astrocytes that are supportive, control the microenvironment, form part of the blood brain barrier and are responsible for gliosis ( fibrosis and scarring of CNS). 2. Oligodendrocytes: their cell membranes form myelin sheath important for insulating nerve impulses thus making transmission quicker 3. Ependymal cells, line the ventricles and spinal cord cavity. 4. Microglia are specialised resident macrophages important for inflammatory and immunologic reaction of CNS.

4 Reaction of neurones to injury Neurones respond to acute injury by changing to red neutrons which appear 12 hours after irreversible insult and characterised by cytoplasmic shrinkage and increased eosinophilia (due to loss of Nissl substance), pyknosis, loss of nucleolus and increased ramifying processes. subacute or chronic neuronal injury causes degeneration and death of neurones, usually by apoptosis (to decrease risk of damaging inflammation). chronic neuronal injury usually affects functionally related neurones

5 Reaction of glial cells to injury glial cells are less vulnerable to acute injury and respond during repair process and gliosis formation. Astrocytes are the main cells involved in repair and respond by forming gemistocytes: hypertophic cells with large eosinophilic cytoplasm, large nuclei and prominent nucleoli glial cells can proliferate while neurones cannot ( although neuronal progenitors have a limited capacity to divide) Microglia respond to injury by: hyperplasia, rod cells, neurophagia and microglial nodule formations.

6 neuropathies of PNS neuropathies are divided to : axonal neuropathy or demyelinating neuropathy 80-90% of neuropathies are axonal The symptoms of both types are related to impaired function of the damaged nerve, and include: Muscle weakness and atrophy,sensory loss,pain, Parasthesia, autonomic dysfunction which might include loss of bowel and bladder control.

7 Diabetic neuropathy is the most common cause of peripheral neuropathy and can manifest as polyneuropathy or mononeuropathy Several forms of neuropathy can occur: 1. distal symmetric sensorimotor polyneuropathy which is the most common form. 2. autonomic neuropathy causing changes in bowel, bladder, or cardiac function 3. Lumbosacral neuropathy causing pain in lower legs. Mechanism of diabetic neuropathies :unknown, probably due to nerve ischemia because of small vessel disease

8 Guillian Barre syndrome is an autoimmune neuropathy. Often follows bacterial viral or mycoplasma infection Can follow immunisation or surgery most commonly after Campylobacter jejuni, CMV, EBV CSF: increased proteins and few WBC Guillian Barrie has two forms: demyelinating, which is the predominant form in USA and Europe, and an immune mediated axonal neuropathy which is more common in Asia

9 Clinical features of Gullian Barre Acute symmetric neuromuscular paralysis often begins distally and ascends proximally Sensory and autonomic disturbances may also occur 5% of patients present with ophthalmoplegia, ataxia and areflexia = if these symptoms exist, it is called Fisher syndrome Muscle paralysis may cause respiratory difficulty, which might cause death. Autonomic involvement may cause cardiac arrhythmia, hypo or hypertension Neuropathy resolves 2-4 weeks after onset and most patients recover

10 axonal regeneration in the PNS Axons of the PNS can regenerate at a rate of 1mm per day. This regeneration can restore function if the injury is mild. More severe injuries need surgical approximation or grafting to improve regeneration. the first step in regeneration is Wallerian degeneration which involves proliferation of Schwann cells that dedifferentiate: they decrease myelin production, phagocytose myelin debris resulting from injury, produce cytokines that stimulate nerve growth and recruit macrophages that also phagocytose debris resulting from the injury. Clearance of the necrotic debris is essential for nerve regeneration. The regeneration is limited by the fact that Schwann cells efficiency decreases after 8 weeks of injury.

11 tumors of the PNS Traumatic neuromas are painful, non neoplastic proliferations of haphazardly arranged axons, Schwann cells and connective tissue, resulting after trauma. Neurofibroma is a benign non encapsulated tumour of Schwann cells mixed with fibroblasts and mast cells Schwannomas are benign encapsulated tumours of Schwann cells. Peripheral nerve sheath tumour is a malignant tumour of Schwann cells. Half of cases are familial ( NF1)

12 NF 1 and NF 2 NF 1 is an autosomal dominant syndrome characterised by multiple neurofibromas, PNST, gliomas and cafe au last skin lesions. NF 1 is caused by a mutation in neurofibromin, an inhibitor of Ras oncogene. NF 2 is characterised by multiple schwannomas ( including acoustic schwannomas that can be bilateral), meningiomas and ependymomas BUT NOT NEUROFIBROMAS. NF 2 is caused by a mutation in merlin protein resulting in loss of contact inhibition.

13 diseases of myelin in the CNS myelin diseases of the CNS are either inherited ( dysmyelinating diseases or leukodystrophies) or acquired ( demyelinating) Demyelination occurs due to autoimmune destruction of myelin ( MS, neuromyelitis optical, post infectious) or due to toxins or chemicals or in iatrogenic settings( central pontine myelinolysis) MS is an autoimmune diseases that occurs in genetically susceptible individuals ( usually with certain polymorphisms in IL2 and IL 7 receptors) and in association with HLA DR 2. Environmental triggers ( viral infections) in genetically susceptible individuals start the symptoms. T helper 2 is stimulated and recruits macrophages, T helper 17 recruits WBCs. These cause inflammatory damage to myelin. the myelin destruction occurs via CD 4 ( helper) and CD8 ( cytotoxic) T cells. B cells also play a role. MS is a white matter diseases, there are sclerotic plaques within the white matter Clinical symptoms of MS vary between individuals and clinical course is unpredictable. Although MS is a diseases of myelin, with time and with recurrent immune and inflammatory response, axonal damage can occur.

14 diseases of myelin in the CNS Neuromyelitis optica is an autoimmune diseases, where myelin is destroyed via antibodies against aquaporine 4. the optic nerve and the spinal cord are the main targets. post infectious demyelination occurs after viral infections and is caused by autoimmune destruction of myelin due to cross reactivity between viral and myelin proteins. clinical symptoms of post infectious demyelination are more severe than MS and patient might die. Survivors retain normal neurological function. Central pontine myelinolysis is an iatrogenic diseases occurring due to rapid correction of hyponatremia which causes disturbed osmotic balance and separation of myelin from axons. the main symptoms are related to motor dysfunction and can cause quardeplegia and locked in syndrome. Dysmyelinating diseases are a group f inherited disorders where children are born normal but develop neurological deficit with age. in these diseases there are mutations in the myelin kinetics ( destruction more than synthesis) or in the myelin proteins themselves. the majority of these are autosomal recessive.

15 Stroke Stroke = CVA, is a clinical term describing acute neurological symptoms caused by vascular disease. stroke can be ischemic or hemorrhagic. Ischemic is commoner Ischemic stroke can be embolic or thrombotic. Embolic is commoner. Most common site of embolic occlusion is the middle cerebral artery. Ischemic strokes might be preceded by TIA= vascular occlusion causing symptoms lasting from minutes to several hours. TIAs predict a full stroke and should be treated promptly. Ischemic infarcts in the brain cause liquefactive necrosis. in the acute stage we see red nuclei and neutrophilic infiltrate in subacute stage we see macrophages,gemistocytes and gliosis. in the late stages, gemistocytes disappear leaving a cavity behind.

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