Personal Notes Gu Neurology PDF

CMS; 511 CEREBROVASCULAR DISORDERS Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F a l l 2 0 2 4 By the end of this session Identify the blood supply of the brain. Causes of cerebral vascular disorder...

CMS; 511 CEREBROVASCULAR DISORDERS Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F a l l 2 0 2 4 By the end of this session Identify the blood supply of the brain. Causes of cerebral vascular disorders. Anterior circulation CVS. Posterior circulation CVS. TIAs. Lacunar CVS. Diagnosis. Treatment. Cerebral blood vessels https://www.msdmanuals.com/professional/multimedia/3dmodel/br ain-vasculature Causes of cerebrovascular stroke (CVS) Stroke is a neurological injury caused by the occlusion or rupture of cerebral blood vessels. Ischemic : Hemorrhagic Both acute ischemic stroke (AIS) Arterial Bleeding from Bleeding into acute Venous occlusion ruptured artery. ischemic stroke. RISK FACTORS Hypertension Hypertension is a major factor in the development of thrombotic cerebral infarction and intracranial hemorrhage. There is no critical blood pressure level; the risk is related to the height of blood pressure and increases throughout the whole range from normal to hypertensive. A 6 mmHg fall in diastolic blood pressure is associated in relative terms with a 40% fall in the fatal and nonfatal stroke rate. Systolic hypertension (frequent in the elderly) is also a significant factor and not as harmless as previously thought. Cardiac disease Cardiac enlargement, failure and arrhythmias, as well as rheumatic heart disease, patent foramen oval and, rarely, cardiac myxoma are all associated with an increased risk of stroke. Diabetes The risk of cerebral infarction is increased twofold in diabetes. More effective treatment of diabetes has not reduced the frequency of atherosclerotic sequelae. Heredity Close relatives are at only slightly greater risk than non-genetically related family members of a stroke patient. Diabetes and hypertension show familial propensity thus clouding the significance of pure hereditary factors. Blood lipids, cholesterol, smoking, diet/obesity These factors are much less significant than in the genesis of coronary artery disease. Race Alterations in life-style, diet and environment probably explain the geographical variations more than racial tendencies. Hematocrit A high blood hemoglobin concentration (or hematocrit level) is associated with an increased incidence of cerebral infarction. Other hematological factors, such as decreased fibrinolysis, are important also. Oral contraceptives Combined oral contraception (COC) containing high dose estrogen increased the risk of thrombosis, including stroke. The effect of low dose estrogen COC is less clear. Anatomy of the cerebral blood vessels= Circle of Willis It is a circle formed of union of 2 anatomical circulation: Anterior: carotid circulation formed of the internal carotid artery and its branches Posterior: vertebrobasilar circulation formed of the 2 vertebral arteries uniting to form the basilar artery. CEREBROVASCULAR DISEASE – NATURAL HISTORY Mechanism of CVS Vascular occlusion Embolization PATHOLOGY Within brain and spinal cord tissue the adventitia is usually very thin and the elastic lamina between media and adventitia less apparent. The intima is an important barrier to leakage of blood and constituents into the vessel wall. OCCLUSIVE AND STENOTIC CEREBROVASCULAR DISEASE The atherosclerotic plaque Following intimal damage: Intimal cells, smooth muscle cells become filled with cholesterol, lipids, phospholipids collagen and elastic fibers subintimally. Hemorrhage may occur within the plaque, or the plaque may ulcerate into the lumen of the vessel forming an intraluminal mural thrombus. Either way, the lumen of the involved vessel is narrowed (stenosed) or blocked (occluded).  The plaque itself may give rise to emboli. Cholesterol is Emboli from present partly in crystal form and fragments following plaques plaque rupture may be sufficiently large to occlude the lumen of distal vessels. The cholesterol esters, lipids and phospholipids each play a role in the aggregation of such emboli. The carotid bifurcation in the neck is a frequent site at which the atheromatous plaque causes stenosis or occlusion.  Platelet emboli arise from thrombus developed over the damaged endothelium. This thrombus is produced partly by platelets coming into contact with exposed collagen fibers. Endothelial cells synthesize PROSTACYCLIN which is a potent vasodilator and inhibitor of platelet aggregation. THROMBOXANE A2, synthesized by platelets, has opposite effects. In thrombus formation these two PROSTAGLANDINS actively compete.  Transient ischemic attacks are episodes of focal TRANSIENT neurological symptoms due to inadequate blood supply to the brain. ISCHAEMIC Attacks are sudden in onset, resolve within 24 hours or less and leave no residual deficit. ATTACKS These attacks are important as warning (TIAs) episodes or precursors of cerebral infarction. Before diagnosing TIAs, consider other causes of transient neurological dysfunction – D.D. migraine, partial seizures, hypoglycaemia, syncope and hyperventilation. The pathogenesis of transient ischemic attacks A reduction of cerebral blood flow below 20– 30 ml/100 g/min produces neurological symptoms. The development of infarction is a consequence of the degree of reduced flow and the duration of such a reduction. If flow is restored to an area of brain within the critical period, ischemic symptoms will reverse themselves. TIAs may be due to: Both mechanisms occur. Emboli are accepted as the cause of the majority of TIAs.  The symptomatology of TIAs Anterior (90%) Posterior (7%) Carotid territory Vertebrobasilar territory hemiparesis, loss of consciousness Hemisensory disturbance, bilateral limb motor/sensory dysphasia, dysfunction monocular blindness binocular blindness (amaurosis fugax) vertigo, tinnitus, not singly, but in diplopia, dysarthria combination with each other Territories of cerebral arteries  OCCLUSION OF THE INTERNAL CAROTID ARTERY May present in a ‘stuttering’ manner due to progressive narrowing of the lumen or recurrent emboli. The degree of deficit varies – occlusion may be asymptomatic and identified only at autopsy, or a catastrophic infarction may result. In the most extreme cases there may be: 1. Deterioration of conscious level 2. Homonymous hemianopia of the contralateral side 3. Contralateral hemiplegia 4. Contralateral hemisensory disturbance 5. Gaze palsy to the opposite side – eyes deviated to the side of the lesion 6. A partial Horner’s syndrome may develop on the side of the occlusion (involvement of sympathetic fibers on the internal carotid wall). 7. Occlusion of the dominant hemisphere side will result in a global aphasia.  Examination of the neck will reveal: Absent carotid pulsation at the angle of the jaw with poorly conducted heart sounds along the internal carotid artery. Prodromal symptoms prior to occlusion may take the form of monocular blindness – AMAUROSIS FUGAX and transient hemisensory or hemimotor disturbance. The outcome of carotid occlusion depends on the collateral blood supply primarily from the circle of Willis, but, in addition, the external carotid may provide flow to the anterior and middle cerebral arteries through meningeal branches and retrogradely through the ophthalmic artery to the internal carotid artery. ANTERIOR CEREBRAL ARTERY (ACA) Anatomy The anterior cerebral artery is a branch of the internal carotid and runs above the optic nerve to follow the curve of the corpus callosum. Soon after its origin the vessel is joined by the anterior communicating artery. Deep branches pass to the anterior part of the internal capsule and basal nuclei. Cortical branches supply the medial surface of the hemisphere: 1. Orbital 2. Frontal 3. Parietal  Clinical features of ACA occlusion The anterior cerebral artery may be occluded by embolus or thrombus. The clinical picture depends on the site of occlusion (especially in relation to the anterior communicating artery) and anatomical variation, e.g. both anterior cerebral arteries (right and left) may arise from one side by enlargement of the anterior communicating artery. Occlusion proximal to the anterior communicating artery is normally well tolerated because of the cross flow between right and left ACA. Distal occlusion results in weakness and cortical sensory loss in the contralateral lower limb. Occasionally a contralateral grasp reflex is present (if prefrontal area is involved) Proximal occlusion when both anterior cerebral vessels arise from the same side results in ‘cerebral’ paraplegia with lower limb weakness, sensory loss,urinary incontinence and presence of grasp, snout and palmomental reflexes Bilateral frontal lobe infarction may result in akinetic mutism or deterioration in conscious level. MIDDLE CEREBRAL ARTERY (MCA) The middle cerebral artery is the largest branch of the internal carotid artery. Passes in the sylvian fissure. It gives off (1) deep branches (perforating vessels – lenticulostriate) which supply the anterior limb of the internal capsule and part of the basal ganglia nuclei. It then passes out to the lateral surface of the cerebral hemisphere at the insula of the lateral sulcus. Here it gives off cortical branches (2) temporal, (3) frontal, (4) parietal. Clinical features of MCA occlusion The middle cerebral artery may be occluded by embolus or thrombus. The clinical picture depends upon the site of occlusion and whether dominant or non- dominant hemisphere is affected. Occlusion at the insula: All cortical branches are involved leading to Contralateral hemiplegia (leg relatively spared) Contralateral hemi anesthesia and hemianopia Aphasia (dominant) Neglect of contralateral limbs Dressing difficulty (non-dominant) When cortical branches are affected individually, the clinical picture is less severe, e.g. involvement of parietal branches alone may produce Wernicke’s dysphasia with no limb weakness or sensory loss. The deep branches (perforating vessels) of the middle cerebral artery may be a source of hemorrhage or small infarcts (lacunes)  CMS; 512 Blood supply of the brain CVS, HEMIPLEGIA Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E O c t o b e r 2 0 2 4 VERTEBRAL ARTERY The vertebral artery and its branches supply the medulla and the inferior surface of the cerebellum before forming the basilar artery. Clinical features of VA occlusion Occlusion of the vertebral artery, when low in the neck, is compensated by anastomotic channels. When one vertebral artery is hypoplastic, occlusion of the other is equivalent to basilar artery occlusion. Only the posterior inferior cerebellar artery (PICA) depends solely on flow through the vertebral artery. Vertebral artery occlusion may therefore present as a PICA syndrome the close relationship of the vertebral artery to the cervical spine is important. Rarely, damage at intervertebral foramina or the atlantoaxial joints following subluxation may result in intimal damage, thrombus formation and embolization. Vertebral artery compression during neck extension may cause symptoms of intermittent vertebrobasilar insufficiency. Stenosis of the proximal left or right subclavian artery may result in retrograde flow down the vertebral artery on exercising the arm. This is commonly asymptomatic and demonstrated incidentally by Doppler techniques or angiography. Occasionally symptoms of vertebrobasilar insufficiency arise – subclavian ‘steal’ syndrome. Surgical reconstruction or bypass of the subclavian artery may be indicated. BASILAR ARTERY The basilar artery supplies the brain stem from medulla upwards and divides eventually into posterior cerebral arteries as well as posterior communicating arteries which run forward to join the anterior circulation (circle of Willis). Branches can be classified into: 1. Posterior cerebral arteries 2. Long circumflex branches 3. Paramedian branches. Clinical features of BA occlusion Prodromal symptoms are common and may take the form of diplopia, visual field loss, intermittent memory disturbance and all other brain stem symptoms: – vertigo – ataxia – paresis – paraesthesia The complete basilar syndrome following occlusion consists of: – impairment of consciousness → coma – bilateral motor and sensory dysfunction – cerebellar signs – cranial nerve signs indicative of the level of occlusion. The clinical picture is variable. Occasionally basilar thrombosis is an incidental finding at autopsy. ‘Top of basilar’ occlusion: This results in lateral midbrain, thalamic, occipital and medial temporal lobe infarction. Abnormal movements (hemiballismus) are associated with visual loss, pupillary abnormalities, gaze palsies, impaired conscious level and disturbances of behavior. Paramedian perforating vessel occlusion gives rise to the ‘LOCKED-IN’ SYNDROME and LACUNAR infarction. POSTERIOR CEREBRAL ARTERY The posterior cerebral arteries are the terminal branches of the basilar artery. Small perforating branches supply midbrain structures, choroid plexus and posterior thalamus. Cortical branches supply the undersurface of the temporal lobe – temporal branch; and occipital and visual cortex – occipital and calcarine branches. Clinical features of PCA occlusion Proximal occlusion by thrombus or embolism will involve perforating branches and structures supplied: Midbrain syndrome – III nerve palsy (LMNL) with contralateral hemiplegia – WEBER’S SYNDROME Thalamic syndromes – chorea or hemiballismus with hemisensory disturbance. Occlusion of cortical vessels will produce a different picture with visual field loss (homonymous hemianopia) and sparing of macular vision (the posterior tip of the occipital lobe, i.e. the macular area, is also supplied by the middle cerebral artery). Posterior cortical infarction in the dominant hemisphere may produce problems in naming, colors and objects. LACUNAR STROKE Occlusion of deep penetrating arteries produces subcortical infarction characterized by preservation of cortical function – language, other cognitive and visual functions. Clinical syndromes are distinctive and normally result from long-standing hypertension. In 80%, infarcts occur in periventricular white matter and basal ganglia, the rest in cerebellum and brain stem. Areas of infarction are 0.5–1.5cm in diameter and occluded vessels demonstrate lipohyalinosis, microaneurysm and microatheromatous changes. Lacunar or subcortical infarction accounts for 17% of all thromboembolic strokes and knowledge of commoner syndromes is essential. LACUNAR STROKE 1. Pure motor hemiplegia Lesion in posterior limb of internal capsule Clinical: Equal weakness of contralateral face, arm and leg with dysarthria Vessel(s): Lenticulostriate A. 2. Pure sensory stroke Lesion in VPL nucleus of thalamus Clinical: Numbness and tingling of contralateral face and limbs. Vessel(s): Thalamogeniculate A. 3. Dysarthria/clumsy hand Lesion in dorsal pons Clinical: Dysarthria due to weakness of ipsilateral face and tongue associated with clumsy but strong contralateral arm. Vessel(s): Perforating branch of Basilar A. 4. Ataxic hemiparesis Lesion in ventral pons (interruption of pontocerebellar fibers) Clinical: Mild hemiparesis with more marked ipsilateral limb ataxia. Vessel (s): Perforating branch of Basilar A. (This syndrome can also be produced by anterior capsular lesions) 5. Severe dysarthria with facial weakness Lesion in anterior limb of internal capsule Clinical: Dysarthria, dysphagia and even mutism occur with mild facial and no limb weakness or clumsiness. Vessel(s): Lenticulostriate A. Sensorimotor syndromes are common. A recent Stroke Data Bank survey showed the commonest presentations to be: - Pure motor hemiplegia 57% - Sensorimotor 20% - Ataxic hemiparesis 10% - Pure sensory 7% - Dysarthria/Clumsy hand 6% Watershed infarctions WATERSHED INFARCTS: ischemic lesions which are situated along the border zones between the territories of two major arteries, for example the anterior and middle or the middle and posterior cerebral arteries Investigations 1. CONFIRM THE DIAGNOSIS Computerized tomography (CT scan) All patients Should have a CT scan, urgently if – conscious level depressed – diagnosis uncertain – on anticoagulants – before commencing/resuming antithrombotic – if thrombolysis is considered. – severe headache at onset. Infarction is evident as a low-density lesion which conforms to a vascular territory, i.e. usually wedge shaped. Subtle changes occur within 3 hours in some patients; most scans become abnormal within 48 hours. CT scan also identifies: – the site and size of the infarct, providing a prognostic guide – the presence of hemorrhagic infarction where bleeding occurs into the infarcted area – intracerebral hemorrhage or tumor. Magnetic resonance imaging (MRI) T2 prolongation (hyperintensity in relation to white and grey matter) occurs within hours of onset of ischemic symptoms. Advanced techniques, diffusion weighted imaging (DWI) and perfusion imaging (PWI) show respectively early infarction (cytotoxic edema) and ischemic tissue at risk (the ischemic penumbra). These advanced techniques are valuable predictors of outcome and guide treatments directed as ‘ischemic salvage’ e.g. thrombolysis. 2. DEMONSTRATE THE SITE OF PRIMARY LESION (a) Non-invasive investigation Ultrasound – Doppler/Duplex scanning: assesses extra- and intracranial vessels. A normal study precludes the need for angiography. Cardiac ultrasound (transthoracic or transesophageal): this often reveals a cardiac embolic source in young people with stroke, e.g. prolapsed mitral valve, patent foramen ovale. Magnetic resonance angiography (MRA) ‘Time of flight’ or contrast enhanced techniques are used. Whilst of value in patients with heavily calcified carotid plaques, resistant to Doppler, it tends to overestimate the severity of stenosis. When assessing the carotid arteries, it is best used in combination with Doppler. Its non-invasive nature makes it helpful in investigating the intracranial circulation. Computed tomographic angiography (CTA) Dynamic helical CT, following bolus injection of non-ionic contrast, can be used to investigate both intracranial and extracranial vasculature. CTA compared with DSA correctly classifies the degree of carotid stenosis in 96% of cases but is insensitive to ulcerative plaque. It is best used in conjunction with Doppler. (b) Digital intravenous subtraction angiography (DSA) The combination of the above techniques has decreased the need for invasive investigation, but cerebral angiography may still be required to make a definitive diagnosis. Management THE ACUTE STROKE Clinical history, examination and investigation will separate infarction and hemorrhage. Once the nature of the ‘stroke’ has been confidently defined, treatment should be instigated. The treatment of stroke has been the subject of many clinical trials and the following is a digest of the current advice based on those studies. Treatment aims – Recanalize the blocked vessels – Prevent progression of present event – Prevent immediate complication – Prevent the development of subsequent events – Rehabilitate the patient. General measures Around the edge of an infarct, ischemic tissue is at risk but is potentially recoverable. This compromised but viable tissue must be protected by ensuring an adequate supply of glucose and oxygen. Factors which might affect this must be maintained – hydration, oxygenation (maintain oxygen saturation over 95%), blood pressure (consider treatment if 185/110), glucose (maintain between 4–11 mmol/l). Treat chest infections and cardiac failure/dysrhythmias. Specific measures Thrombolysis Intravenous recombinant tissue plasminogen activator (alteplase) given within 3 hours of an anterior circulation ischemic stroke improves outcome despite the increased risk of iatrogenic intracranial hemorrhage. Thus, patients who might be candidates need urgent assessment and CT scanning to exclude cerebral hemorrhage. Patients not eligible for thrombolysis Give aspirin 300 mg daily for 2 weeks or clopidogrel in aspirin intolerant patients. Anticoagulants should be avoided if possible as they increase the risk of deterioration from hemorrhagic transformation. Transfer to stroke unit There is good evidence that multidisciplinary care on a stroke unit improves the outcome of patients with stroke. Outcome of CVS Approximately one-third of all ‘strokes’ are fatal. The age of the patient, the anatomical size of the lesion, the degree of deficit and the underlying cause all influence the outcome. Immediate outcome In cerebral hemorrhage, mortality approaches 50%. Cerebral infarction is better, with an immediate mortality of less than 20%, fatal lesions being large with associated edema and brain shift. Embolic infarction carries a better outcome than thrombotic infarction. Fatal cases of infarction die either at onset, early within a few days because of cytotoxic cerebral edema or later from cardiovascular or respiratory complications. The level of consciousness on admission to hospital gives a good indication to immediate outcome. The deeper the conscious level the graver the prognosis. Outcome of CVS Long-term outcome The prognosis following infarction due to thrombosis or embolization from diseased neck vessels or heart is dependent on the progression of the underlying atherosclerotic disease. Recurrent cerebral infarction rates vary between 5% and 15% per year. Symptoms of coronary artery disease and/or peripheral vascular disease may also ensue. Five-year mortality is 44% for males and 36% for females. The long-term prognosis following survival from hemorrhage depends upon the cause and the treatment. GOOD LUCK Clinical approach to speech disorders Disturbances of speech and communication have different presentations according to: The type The onset The course The duration Types of speech disorders Dysphasia (aphasia) Dysarthria (anarthria) Upper motor neuron lesion Lower motor neuron lesion Results from brain (motor and Brainstem motor nuclei lesions sensory areas) and bilateral Articulation of speech affected brainstem tract lesions. with intact comprehension and Comprehension and / or expression. expression affected Types of dysphasia (aphasia) Types of dysarthria Flaccid dysarthria. Flaccid dysarthria is caused by lower motor neuron damage.... Spastic dysarthria.... Unilateral upper motor neuron dysarthria.... Ataxic dysarthria.... Hypokinetic dysarthria.... Hyperkinetic dysarthria.... Mixed dysarthria. Types of dysarthria The onset of speech disorder The time in which all symptoms in the patient HPI occurred 1. Acute: (seconds- hours- days) Dramatic (seconds- minutes) Sudden (hour- 24 hours) Rapid (day – 4-5 days) 2. Subacute (one- two weeks) 3. Chronic – progressive- (2 weeks and more) The course of speech disorder Regressive Stationary Intermittent Remittent Progressive The duration of speech disorder Day (s) Week (s) Month (s) Year (s) Diagnosis of the cause What is the lesion? Treatment Of the cause Specialized speech assessment Speech therapy GOOD LUCK  CMS; 511 Peripheral Neuropathy Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4 This lecture will address Nerve structure and lesion. The different clinical presentations and causes of neuropathy. The clinical picture, investigations, differential diagnosis, and treatment of Guillain Barre syndrome. Approach to a patient with neuropathy. Neuropathy Damage or dysfunction of a nerve or more causing characteristic symptoms and signs The lower motor system Anterior horn cells. Roots and Plexus. Peripheral nerves. Myoneural junction. Muscles. What is a nerve (peripheral nerve) ? A nerve or a peripheral nerve is the part of the lower motor system that starts from the anterior horn cell, root, plexus and peripheral nerve proper. Nerves are cranial (12) and spinal (31) Nerves are heavily myelinated, thinly myelinated and unmyelinated Nerves are motor, sensory, autonomic and mixed. Nerve structure The nerve basic functions are based on 3 components; myeline sheath, axon and vasa nervosum Myelin allows for insulation and rapid conduction of nerve impulses. Lesion causes demyelination neuropathy. Axons are the actual nerve “wires” that conduct the electrical signals. Lesion causes axonal neuropathy. Blood vessels (vasa nervosa) carry nutrients to the nerves and waste products away from them. Lesion causes axonal neuropathy. Symptoms of peripheral neuropathy (PN) Motor Sensory Positive symptoms ; Positive symptoms; tremors , cramps, and due to nerve irritation; fasciculations. tingling, pain, pins - needles, Negative symptoms; and itching. weakness, heaviness, and gait Negative symptoms: abnormalities. representing loss of function; numbness, tremors and gait abnormalities. Autonomic dysfunction. Signs of PN Sensory: hypoesthesia (superficial-deep) in the distribution of the affected nerve(s) Motor: muscle wasting, hypotonia and weakness of muscles supplied by the affected nerve(s). In polyneuropathy; bilateral, distal more than proximal. Autonomic: skin dryness, loss of sweating, loss of hair, and trophic ulcers. Where is the lesion in neuropathy ? Neuropathy may present as : Mononeuropathy. Mononeuropathy multiplex. Polyneuropathy. Plexopathy. Where and what is the lesion in mononeuropathy ? Acute Bell`s palsy: cold exposure induced, head or facial surgery Trauma: fracture long bones; radial peroneal,…. Cut injuries: glass, sharp objects. Diabetes mellitus (DM): vascular ischemia; facial, abducent and oculomotor nerves. Chronic: nerve entrapment Median nerve at the wrist (carpal tunnel syndrome) Ulnar nerve at the elbow (cubital syndrome) Lateral cutaneous nerve at the inguinal ligament Bell`s palsy The most common cause of acute mononeuropathy. 1. Unilateral Idiopathic; cold exposure induced. DM. Trauma,… 2. Bilateral GBS, Para malignant S., Sarcoidosis,.. Carpal tunnel syndrome (C.T.S)  C.T.S The first most common entrapment compression neuropathy. Females more than males, manual workers, caused by frequent flexion of the wrist. Starts unilateral, then becomes bilateral. Median nerve; 3.5 fingers manifestations (sensory and motor) in thenar region. Nerve conduction delay distal latencies (M&S) and decreased SNCV with normal MNCV. Double crush injuries???  Treatment Rest Brace of wrist Medication Stretch exercises Surgical; median nerve decompression. Cubital tunnel syndrome Cubital.T.S (cell phone S) The second most common entrapment in the upper limb. Full flexion at the elbow, with extension of the wrist, or following injuries to the elbow by fractures or dislocation. Sensory; tingling, pain and weakness of hypothenar and small muscles of hand. Treatment Rest Brace of elbow Medication Surgical; ulnar nerve decompression. Where and what is the lesion in mononeuropathy multiplex ? Acute: Diabetes mellitus. Multifocal motor neuropathy vasculitis Chronic: Cervical and lumbar spondylosis Sarcoidosis. Leprosy. AIDS. Where and what is the lesion in polyneuropathy ? Acute: Diabetes mellitus. Guillain Barre syndrome Chronic: Diabetes mellitus. Paraneoplastic syndrome. Chemotherapy. Vit B12 deficiency, alcoholism. Heavy metal toxicity, porphyria. Hereditary polyneuropathy; sensory-motor (CMT), pure sensory, and sensory-autonomic types. (CMT: Charcot-Marie-Tooth) Where and what is the lesion in plexopathy ? Acute: Trauma; fracture clavicle (brachial px) fracture pelvis (lumbar px). Birth injury Diabetes mellitus. Chronic: Diabetes mellitus. Local tumors in the pelvis or pleura or apical lung region  Erb`s palsy and Klumpke`s palsy Lesion of upper trunk of brachial plexus Lesion of lower trunk of brachial plexus affecting radial, axillary and affecting ulnar and median nerves due to musculocutaneous nerves due to traction of traction of arm in abduction position head or lateral flexion of neck Anterior horn cell disorders The combination of weakness, hypotonia and fasciculations are suggestive of AHCs disease. Causes: Degenerative; spinal muscular atrophy (SMA) syndromes, the most seen in infancy is type I SMA (Werdnig-Hoffman Disease) onset in the first 6 months of life. Other 4 types are less common, may benefit new genetic modulation medication Viral; poliomyelitis was the most common in infancy and childhood, had predilection to AHCs infection. Guillain-Barre syndrome (GBS) Autoimmune disease attaching nerve roots and peripheral nerves. It is the commonest cause of acute flaccid paralysis. (After the introduction of oral polio vaccine (OPV)) Mixed motor (proximal), sensory (peripheral) and autonomic polyneuropathy. Bilateral facial LMNL The classic presentation is characterized by an acute monophasic, non-febrile, postinfectious illness manifesting as ascending weakness and areflexia. Brainstem abnormalities may also be seen. Pathophysiology Roughly two thirds of patients have a history of an antecedent gastrointestinal or respiratory tract infection. Some of the pathogenic triggers of GBS include Epstein-Barr virus, cytomegalovirus, enteroviruses, hepatitis A and B, varicella, Mycoplasma pneumoniae, and Campylobacter jejuni, which is the most common. Resemblance of the triggering pathogens to antigens on peripheral nerves (ie, molecular mimicry) leads to an autoimmune response mounted by T-lymphocytes and macrophages. Most of these patients have antibodies against the GQ1b ganglioside. Subtypes of GBS GBS peripheral nerve damage can be classified histopathologically into 2 main types: demyelinating forms and axonal-degenerating forms. GBS was subdivided into 4 distinct forms based on histopathological and neurophysiological basis: 1. acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 2. acute motor axonal neuropathy (AMAN), 3. acute motor and sensory axonal neuropathy (AMSAN), 4. and Miller-Fisher syndrome (MFS). Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) This accounts for 80-90% of GBS cases in Europe and North America. It is an immune-mediated attack of myelin with infiltration of lymphocytes and macrophages with segmental demyelination. Both humoral and cell-mediated immune response Motor and sensory fibers are usually affected simultaneously, producing corresponding deficits. Electrophysiology shows slow nerve conduction velocity and prolonged F waves. Acute motor axonal neuropathy (AMAN) This form of neuropathy is the most seen in China and Japan (50- 60% of cases), as apposed to Western countries (10-20% of cases). In this form, axonal degeneration occurs by immune attack within 1-2 weeks after infection. Specific antibodies to axonal membranes of motor fibers attack the nodes of Ranvier. This, in turn, activates complement and intrusion of macrophages into periaxonal space, resulting in destruction of axons. C jejuni is the most common preceding infection, and antiganglioside antibodies are usually found in this type. Electrophysiology shows reduction in muscle action potentials with relatively preserved motor nerve conduction velocity and normal sensory nerve action potentials and F waves. Miller-Fisher syndrome (MFS) The involvement of CNs is very distinct in this form of GBS. Ocular motor nerves (oculomotor, trochlear, and abducens) are affected and produce a triad of ophthalmoplegia, ataxia, and areflexia. Electrophysiology is normal. The characteristic autoantibodies are against gangliosides GQ1b and GT1a. GQ1b plays a key role in the pathogenesis of MFS Acute motor and sensory axonal neuropathy (AMSAN) This type is rare and resembles AMAN except that sensory nerves are also affected. This type is associated with a severe course and poor prognosis. Other rare variants of GBS Polyneuritis cranialis - This is an acute onset of multiple CN palsies (usually bilateral CN VII with sparing of CNs I and II), elevated cerebrospinal fluid protein, and slowed nerve conduction velocity with uncomplicated recovery. Pharyngo-cervical-brachial syndrome - This variant form of GBS is characterized by localized and regional involvement of autonomic and motor nerves in the pharyngeal-cervical- brachial distribution. The diagnosis of this condition is based on clinical, laboratory, and neurophysiological findings and the exclusion of other conditions mimicking this disorder. Acute sensory neuropathy of childhood Acute pandysautonomia is also a common subtype with which the autonomic nervous system is involved. Parasympathetic and sympathetic involvement is seen along with sensory or motor nerve involvement. Physical Examination An ascending motor weakness is noted along with areflexia in the classic form. Areflexia is a hallmark of GBS. However occasionally, some of the more proximal reflexes still may be elicited during the early phase of the disease. Autonomic instability (26%), ataxia (23%), dysesthesias (20%), and cranial nerve findings (35- 50%), predominantly facial palsy. Bilateral facial palsy are more frequent cranial nerves involved with this syndrome. Physical Examination Leg weakness (ie, foot drop) is usually noticed first, and weakness eventually involves the calves and thighs. Later, trunk muscles and upper extremities show involvement. Weakness also may involve the respiratory muscles, and some patients need respiratory support during the course of the disease. Mechanical ventilation is used until respiratory muscle function returns The autonomic neuropathy manifestations include orthostatic hypotension, hypertension, pupillary dysfunction, sweating abnormalities, and sinus tachycardia. Diagnosis Based on progressive ascending weakness with areflexia. Nearly 2 weeks after presentation of symptoms, lumbosacral MRI can show enhancement of the nerve roots with gadolinium. This imaging study has been described to be 83% sensitive for acute GBS, with nerve root enhancement present in 95% of typical cases. LP findings are suggestive of demyelination (ie, increased protein >45 mg/dl within 3 weeks of onset) without evidence of active infection (lack of CSF pleocytosis). The CSF findings may be normal within the first 48 hours of symptoms, usually by 10 days of symptoms, elevated CSF protein findings will be most prominent. Most patients have fewer than 10 leukocytes per milliliter. Greater than 50 mononuclear cells/mL of CSF makes the diagnosis of GBS doubtful. Differential Diagnosis Other causes of polyneuropathy (see above). Other causes of bilateral facial palsy; sarcoidosis and paraneoplastic syndrome: subacute or chronic illness. Other causes of neuromuscular weakness 1. Newly acquired neuromuscular weakness in intensive care unit (ICU) patients consist of critical illness polyneuropathy (CIP). 2. Critical illness myopathy 3. Drug induced neuromuscular weakness which may arise in: i. consequence of sepsis. ii. multi-organ failure iii. exposure to certain medications like intravenous corticosteroids and neuromuscular blocking agents. Electrodiagnostic Studies Within the first week of the onset of symptoms, electrodiagnostic studies in at least two limbs reveal the following: A dispersed, impersistent, prolonged, or absent F response (88%) Increased distal latencies (75%) Nerve conduction block (58%) or temporal dispersion of compound muscle action potential (CMAP) Reduced conduction velocity (50%) of motor and sensory nerves Criteria for axonal forms include lack of neurophysiologic evidence of demyelination, with loss of amplitude of CMAP or sensory nerve action potentials to at least less than 80% of lower limit of normal values for age. If electrical studies are performed too early, normal results can be falsely reassuring. By the second week of illness, reduced compound muscle action potential (CMAP, 100%), prolonged distal latencies (92%), and reduced motor conduction velocities Serum Anti-Ganglioside Antibodies Serum ganglioside antibodies directed against GM1, GM1b, GD1a, and GalNAc-GDIa have been associated with Campylobacter jejuni infection. Those with positive antibodies had a more prolonged recovery with more residual symptoms. GQ1b with Miller-Fisher syndrome, GD1b with acute sensory neuronopathy, GT1a with pharyngeal-cervical-brachial variant. Assays for these antibodies may be useful in the diagnostic workup of variant clinical presentations. Treatment Treatment for Guillain-Barré syndrome (GBS) has been aimed primarily at immunomodulation. Plasmapheresis is started immediately once suspected GBS. Intravenous immunoglobulin (IVIG) is the most effective form of therapy in pediatrics and used as a second line of treatment after poor response of plasmapheresis in adults. Corticosteroids were previously used to treat GBS, but current data indicate they provide little benefit. Physiotherapy from start of weakness Neurotropic medications for sensory symptoms. Approach to a patient with neuropathy Proper history and examination to diagnose; mono or polyneuropathy or other types. Diagnose the possible cause; autoimmune, metabolic, toxic, drug induced or other causes. Initial evaluation of a patient with neuropathy should include a complete blood count, comprehensive metabolic profile, and measurement of ESR, FBS, vit B12, and TSH. Electrodiagnostic studies are recommended if symptoms persist and if the diagnosis remains unclear after initial diagnostic testing and a careful history and physical examination. Options for symptomatic treatment of peripheral neuropathy include low doses of antiseizure medications, tricyclic antidepressants, and topical medications. Thank you  CMS; 511 Muscle Disorders Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4  This lecture will address The different causes of myopathies as muscular dystrophies, myositis, toxic and metabolic myopathy Pathophysiology, clinical picture, investigations, and treatments of myasthenia gravis  Normal skeletal muscle structure A skeletal muscle is composed of large number of muscle fibers separated by connective tissue (endomysium) and arranged in bundles (fasciculi) in which the individual fibers are parallel to each other. Each fasciculus has a connective tissue sheath (perimysium) and the muscle itself is composed of number of fasciculi bound together and surrounded by a connective tissue sheath (epimysium). Essentials for diagnosis Weakness, generally more proximal than distal Skeletal muscles generally affected, may be cardiac muscle Normal sensations Normal sphincter function Relative preservation of deep tendon reflexes Positive laboratory tests to support the diagnosis Electromyography is essential tool of diagnosis Muscle biopsy and genetic testing offer definitive diagnosis. Classification of myopathies Hereditary Acquired Congenital myopathies Inflammatory/ immune- Muscular dystrophies mediated myopathies Myotonias Drug induced myopathies Channelopathies Toxic myopathies Metabolic myopathies Myopathies due to systemic illness Mitochondrial myopathies Endocrine myopathies Infectious myopathies Acquired Myopathies Acquired Inflammatory myopathies Polymyositis Dermatomyositis Inclusion body myositis Sarcoid myopathy Infectious myopathy. Polymyositis Myopathic distribution of weakness Age at onset: any age Muscle pains and tenderness Spontaneous EMG activity Elevated CK level Presence of myositis antibodies Muscle biopsy; endomesial infiltration of inflammatory cells. Dermatomyositis Myopathic distribution of weakness Age at onset any age Muscle pains and tenderness Characteristic skin lesions, see photos. Spontaneous EMG activity Markedly elevated CK level Presence of myositis antibodies Muscle biopsy; perivascular and peri-mesial infiltration of inflammatory cells with perifascicular atrophy. V sign: Erythematous rash around face, neck Shawl sign: erythematous rash affecting upper back and anterior chest Gottron’s papules are red, scaly papules that occur over the dorsal aspect of the metacarpophalangeal, proximal and distal interphalangeal joints Dilated capillary loops in the nail bed and small ulceration involving the distal aspect of the little finger Gottron’ssign is the same red, scaly papularrash occurring elsewhere on the body Inclusion body myositis (IBM) IBM is a condition characterized by both inflammatory and degenerative changes within the muscle. IBM occurs in patients aged over 50 years. The muscle weakness pattern is notable for both proximal and distal involvement with asymmetry being a common feature. The pattern of muscle weakness particular to IBM is early involvement of the finger flexors, ankle dorsiflexors and knee extensors. (distal followed by proximal). Head drop may manifest due to axial muscle involvement. Dysphagia occurs in over half of all patients with IBM. Inclusion body myositis (IBM) The condition follows a slowly progressive coarse and is unresponsive to immunotherapy. High degrees of disability are seen, especially due to falls and weakness of grip Muscle biopsy shows Features of chronic myopathy with endomysial lymphocytic infiltration Lymphocytic and rimmed vacuoles are infiltration characteristic. Rimmed vacuoles Infectious myopathies Viral myositis; influenza, enteroviruses, retroviruses,… Fever, myalgias and weakness, highly elevated CK, myoglobinuria, may be renal failure Bacterial myositis; (pyomyositis) may occur in DM, IV drug abusers, skin infarctions, malignancy, muscle trauma, present by fever, myalgias, focal or severe muscle weakness, elevated CK, Parasitic myositis; Fever, myalgias and proximal weakness, elevated CK, eosinophilia in CBC HIV-associated myopathy. Drug induced or toxic myopathies Corticosteroid myopathy History of long duration intake of corticosteroids Slowly progressive proximal weakness, rapid course in some cases cushingoid features, normal CK level, EMG may be normal Muscle biopsy; type 2b fiber atrophy Cholesterol lowering agent myopathy Myopathy in critical illness seen in ICU. Secondary metabolic myopathies Hypokalemic myopathy; weakness myalgia, k chronic lesion O/E positive rebound (ULs) Pendular knee jerk (LLs)  Incoordination Abnormalities of intended (volitional) movement. Dyssynergia, dysmetria and dysdiadochokinesis. Abnormality of rate, range and force of movement. Slowing of initiating movement, irregular and slow movement acceleration and deceleration w increase on reaching the target. The force and velocity of movement is not checked normally, the limb overshoots the target (hypermetria) due to delayed activation of antagonist muscles, the movement is corrected by series of secondary movement in which a finger sways around the target or moves side to side on the target itself (intention tremors). Incoordination Titubation Tremors of 3-4/s of head and upper trunk anteriorly. Explosive speech slow interrupted speech with less or more force than normal (stacatto dysartheria). Ocular movement Conjugate voluntary gaze ends by jerky movements on attempted fixation (saccadic dysmetria=nystagmus). Smooth pursuit movement are impaired by catch up saccades to keep following the movement. What causes ataxia? Acute transitory Acute reversible Acute enduring Subacute (weeks) Chronic (months or years) Acute transitory Intoxication by: Medications overdose; Phenytoin, barbiturates, lithium ,alcohol. Diamox responsive episodic ataxia Metabolic; Childhood hyperammonemias Acute reversible Postinfectious cerebellitis, mostly varicella (after infection or vaccination), EBV, enteroviruses, parvovirusB19; 5-10 days after prodroma, mild changes in CSF, full recovery 10-20 days. Viral (direct) cerebellar encephalitis Acute enduring Cerebellar infarction, hemorrhage, trauma. Acute Demyelinating Encehalomyelitis(ADEM). Hyperthermia with coma at onset Intoxication with mercury compounds or toluene (glue sniffing) spray painting Subacute (weeks) Multiple sclerosis Miller -Fisher varient of GBS (oculomotor palsy, areflexia, bulbar more than limb weakness+ataxia (selective peripheral spinocerebellar fibers). Brain tumors ; medulloblastoma, astrocytoma, hemangioblastoma (w haedache and papilledema) Alcohol; nutritional Paraneoplastic; opsoclonus, specific anticerebellar anti bodies (breast and ovarian carcinoma). Cerebellar abscess, history of middle ear infection. Chronic (months or years) Malnutrition; vitamin B12 defiency. Hypothyroidism. Hydrocephalus. Friedreich ataxia Spinocerebellar degenerations; olivopontocerebellar degeneration, cerebellar cortical degeneration Hereditary metabolic diseases, often with myoclonus. Childhood ataxia; ataxia telangictasia, cerebellar agenesis, other genetic ataxia Degenerative ataxia Ataxia mostly inherited Genetic ataxia sex linked the DNA and gene is located on an X or Y chromosome (the sex chromosomes). autosomal linked, abnormality is located on one of the other 23 pairs of chromosomes. Spinocerebellar and episodic ataxias are autosomal dominant ataxias. Friedreich ataxia and ataxia talangectasia are autosomal recessive. Spinocerebellar ataxia (SCA) a group of hereditary ataxias that are characterized by degenerative changes in the cerebellum, and in the spinal cord. There are many different types of SCA, and they are classified according to the mutated(altered) gene responsible for the specific type of SCA. The types are described using "SCA" followed by a number, according to their order of identification: SCA1 through SCA40 and more. The signs and symptoms may vary by type but are similar, and may include an uncoordinated walk (gait), poor hand-eye coordination, and abnormal speech (dysarthria). SCA is inherited in an autosomal dominant manner. However, the term "spinocerebellar" may be found with other diseases, such as the autosomal recessive spinocerebellar ataxias (SCAR). Less common causes Wilson`s disease is autosomal recessive affecting the body's ability to metabolize copper and may lead to ataxia. It is an example of why classifying ataxia is sometimes difficult, since it is both a genetic and structural cause. There are a group of patients with ataxia where the cause is not found and this ataxia is classified as idiopathic ataxia. Celiac disease is an immune-mediated illness and is often thought only as a digestive disorder where the body cannot digest gluten. However, it may affect many other organs in the body. Gluten-associated ataxia may be one of the causes of sporadic idiopathic ataxia. Differential diagnosis Sensory ataxia Severe sensory neuropathy (gloves & stalking) Absent other cerebellar signs (nystagmus & dysarthria) Gait is wide base stamping feet with irregular short or long , forwards or outward the patient looking to the ground to correct for the absent sense of position The patient sways when standing with feet together with eyes closed; positive Romberg`s sign. Seen in diseases of posterior columns and affected proprioceptive sensation; DM, vit B12 def. Vestibular ataxia Main complain is vertigo Evident past-pointing test Rotatory, vertical and mixed nystagmus History of streptomycin toxicity Thalamic ataxia Infarction or hemorrhage of anterior thalamus May be transient Accompanied by contra lateral signs. Superior parietal lobule(area 5&7) Contra lateral ataxia, similar to cerebellar ataxia.  Diagnosis Onset of symptoms; acute, subacute, chronic. An altered conscious state, Focal neurologic sign, Meningism, Posterior column sensory loss, Signs of raised intracranial pressure, History malnutrition, drug intake, intoxication Family history, similar cases. CSF analysis, serum drug level. MRI and MRA, contrast in autoimmune and infection. Treatment Antiviral, antibiotics. Vitamin and hormonal replacement CVS MS Plasma pharesis IVIgs Surgery Thank you  CMS; 511 EPILEPSY & STATUS EPILEPTICUS 33 Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4  1-Definition of epilepsy. 2-Different types of seizures. 3-Different types of epilepsy. ILOs 4-Lines of management of epilepsy. 5-Conventional antiepileptic drugs. (Indications and side effect) 6- Status epilepticus  Definition of Terms Spell Seizure Epilepsy Spell (or event or attack) is a noncommittal (honest) term used when the nature of an attack is uncertain. Is it a seizure or a seizure equivalent? Is the seizure really a generalized or a focal brain disturbance? Seizure Is a paroxysmal disturbance of brain electrical activity. Seizure types are classified based on both EEG and behavioral changes during a seizure. 8-10% of the population will have a seizure by age 80, 4-5% by age 20, 3-4% by age 6 will have a febrile seizure. Epilepsy Is recurrent unprovoked seizures. Prevalence, or percent of the population actively experiencing recurring seizures, varies from 0.2 - 1%, usually 0.7%. In other words, most seizures do not recur, and those that do often do not persist. Epileptic Syndrome is a characteristic clinical constellation of one or more seizure types, + certain EEG, genetic, pathological or prognostic features. Unlike disease, it may not have uniform etiology and prognosis. CAT scans, MRI scans, PET scans, interictal EEGs, psychological tests, etc. cannot determine that certain behavior is a seizure. They may help define the seizure type and syndrome and therefore the treatment and prognosis. ILAE OFFICIAL REPORT Epilepsy is a disease of the brain defined by any of the following conditions 1. A leasttwo unprovoked (or reflex) seizures occurring >24 h apart 2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years 3. Diagnosis of an epilepsy syndrome Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years. Definition A seizure is an abnormal, hypersynchronous discharge of cortical neurons, and epilepsy is defined as a propensity to have seizures. A diagnosis of epilepsy is considered in the following circumstances: 1. Two unprovoked seizures more than 24 hours apart 2. One unprovoked seizure but with a high recurrence risk (60% and over) 3. A diagnosis of an epilepsy syndrome. Seizure Types Classifications Epilepsy Classifications  Localization-related seizures, arise from an epileptic focus, (a small portion of the brain that serves as the irritant driving the epileptic response.)  Generalized seizures, in contrast, arise from many independent foci (multifocal epilepsies) or from epileptic circuits that involve the whole brain. Originate at some point within and rapidly engage bilaterally distributed networks Can include cortical and subcortical structures but not Epilepsy Syndromes Epilepsy syndromes are further divided by hypothetical cause: idiopathic, symptomatic,. Idiopathic epilepsies are thought to arise from genetic abnormalities that lead to alteration of basic neuronal regulation. Symptomatic epilepsies arise from the effects of an epileptic lesion, whether that lesion is focal, such as a tumor, or a defect in metabolism causing widespread injury to the brain. Epilepsies attributed to structural-metabolic causes (symptomatic) Tumor Infection Trauma Angioma Peri-natal insults Stroke,Etc. Just as there are many types of seizures, there are many types of epilepsy syndromes. Each type of epilepsy syndrome presents with its own unique combination of : Seizure type, Typical age of onset, EEG findings, Treatment, and Prognosis. Generalized epilepsy syndromes Childhood absence epilepsy (CAE) Is an idiopathic generalized epilepsy that affects children between the ages of 4 and 12 years of age, although peak onset is around five to six years old. These patients have recurrent absence seizures, brief episodes of unresponsive staring, sometimes with minor motor features such as eye blinking or subtle chewing. The EEG finding in CAE is generalized 3 Hz spike and wave discharges.  It is more common in girls than boys Some go on to develop generalized tonic-clonic seizures. This condition carries a good prognosis because children do not usually show cognitive decline or neurological deficits, and the seizures in the majority cease spontaneously with ongoing maturation. Spike and wave  Childhood absence epilepsy (CAE) Seizures are believed to originate in the thalamus, where there is an abundance of calcium channels. Treatment of patients with absence seizures only is mainly with ethosuximide, or sodium valproate which are of equal efficacy controlling absences in around 75% of patients  Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy that occurs in patients aged 8 to 20 years. Patients have normal cognition and are otherwise neurologically intact. The most common seizures are myoclonic jerks, although generalized tonic-clonic seizures and absence seizures may occur as well. Myoclonic jerks usually cluster in the early morning after awakening. The EEG reveals generalized 4–6 Hz spike wave discharges or multiple spike discharges.  These patients are often first diagnosed when they have their first generalized tonic-clonic seizure later in life, when they experience sleep deprivation. Alcohol withdrawal can also be a major contributing factor in breakthrough seizures, as well. The risk of the tendency to have seizures is lifelong; however, the majority have well-controlled seizures with anticonvulsant medication and avoidance of seizure precipitants. Epilepsy with generalized tonic-clonic seizures alone (GTC) Formerly known as (grand mal seizures) Is type of generalized seizure that affects the entire brain. Tonic–clonic seizures are the seizure type most commonly associated with epilepsy and though it is a misconception that they are the only type. Phases GTCs Tonic phase: The person will quickly lose consciousness, and the skeletal muscles will suddenly tense, often causing the extremities to be pulled towards the body or rigidly pushed away from it, which will cause the person to fall if standing. The tonic phase is usually the shortest part of the seizure, usually lasting only a few seconds. The person may also express vocalizations like a loud scream during the tonic stage, due to air forcefully expelled from the lungs. Clonic phase The person's muscles will start to contract and relax rapidly, causing convulsions. These may range from exaggerated twitches of the limbs to violent shaking or vibrating of the stiffened extremities. The eyes typically roll back and the tongue often suffers bruising (bitting) by sustained strong jaw contractions. Incontinence is seen in some cases Post ictal phase Due to physical and nervous exhaustion, Postictal sleep invariably follows a tonic–clonic seizure. Confusion and complete amnesia upon regaining consciousness is usually experienced. Localization related epilepsy syndromes  Temporal lobe epilepsy (TLE) A symptomatic localization-related epilepsy, Is the most common epilepsy of adults who experience seizures poorly controlled with anticonvulsant medications. In most cases, the epileptogenic region is found in the midline (mesial) temporal structures (e.g., the hippocampus, amygdala, and parahippocampal gyrus). Seizures begin in late childhood and adolescence. Most of these patients have complex partial seizures sometimes preceded by an aura, and some TLE patients also suffer from secondary generalized tonic-clonic seizures. If the patient does not respond sufficiently to medical treatment, epilepsy surgery may be considered.  TLE Presentations Ascending epigastric sensation or visceral aura. Ictal Fear. Oro-alimentary automatisms. Disturbed conscious level. Partial amnesia. Fugue.  Uncinate fits A form of temporal lobe epilepsy in which hallucinations of taste and smell and inappropriate chewing movements are prominent features.  Febrile seizures A febrile seizure, also known as a fever fit or febrile convulsion, is a convulsion associated with a significant rise in body temperature. They most commonly occur in children between the ages of 6 months and 6 years and are twice as common in boys as in girls A febrile seizure is the effect of a sudden rise in temperature (>39°C) rather than a fever that has been present for a prolonged length of time Types A simple febrile seizure is one in which - The seizure lasts less than 15 minutes (usually much less than this), - Does not recur in 24 hours, - Involves the entire body (classically a generalized tonic-clonic seizure). A complex febrile seizure is characterized by - longer duration, recurrence, or focus on only part of the body. The simple seizure represents most cases.  Prognosis Children with febrile convulsions are more likely to suffer from a febrile epileptic attacks in the future if they have 1- a complex febrile seizure, 2- a family history of afebrile convulsions in first-degree relatives (a parent or sibling), or 3- a preconvulsion history of abnormal neurological signs or developmental delay. Causes related epilepsy The diagnosis of epilepsy usually requires that the seizures occur spontaneously, however; Reflex epilepsy: primary reading epilepsy have seizures triggered by reading. Photosensitive epilepsy limited to seizures triggered by flashing lights. Precipitants can trigger an epileptic seizure in patients who otherwise would be susceptible to spontaneous seizures. For example, children with childhood absence epilepsy may be susceptible to hyperventilation. Other precipitants can facilitate seizures in susceptible individuals: Emotional stress, sleep deprivation, sleep itself, alcohol and febrile illness. Catamenial epilepsy (CE) is when seizures cluster around certain phases of a woman's menstrual cycle. Pathophysiology Mutations in several genes have been linked to some types of epilepsy. Several genes that code for protein subunits of voltage-gated and ligand- gated ion channels have been associated with forms of generalized epilepsy and infantile seizure syndromes. e.g. mutations of the genes that code for sodium (Na)channel proteins; These defective sodium channels stay open for too long, thus making the neuron hyper-excitable. Glutamate, an excitatory neurotransmitter, may, therefore, be released from these neurons in large amounts, which triggers excessive calcium (Ca 2+) release in the post-synaptic cells. Such excessive calcium release can be neurotoxic to the affected cell. Another possible mechanism involves mutations leading to ineffective GABA action, (the brain's most common inhibitory neurotransmitter). Management Management Epilepsy is usually treated with medication. Accurate differentiation between generalized and partial seizures is especially important in determining the appropriate treatment. In some cases the implantation of a stimulator of the vagus nerve, or a special diet (keto diet) can be helpful. Neurosurgical operations for epilepsy can be palliative, reducing the frequency or severity of seizures; or, in some patients, an operation can be curative.  Antiseizure Medications (ASM) Anticonvulsant: The mainstay of treatment of epilepsy is anticonvulsant medications. The choice among anticonvulsants and their effectiveness differs by epilepsy syndrome. Availability - Currently there more than 20. Conventional antiepileptic : Epanutin Tegretol Depakine Phenobarbiturate. New antiepileptic : others. A-Sodium Channel Blockers Sodium channel blockade is the most common and best- characterized mechanism of currently available antiepileptic drugs (AEDs). AEDs that target sodium channels prevent the return of the channels to the active state by stabilizing the inactive form. So, repetitive firing of the axons is prevented. and reduces the spread of seizures. 1- Carbamazepine (Tegretol). 2- Phenytoin (Epanutin). 3-Oxcarbazepine (Trileptal ). 4-Lamotrigine (Lamictal). Carbamazepine (Tegretol) Carbamazepine (CBZ) is a major first-line AED for partial seizures and generalized tonic-clonic seizures. Potential dose-related adverse effects include: dizziness, diplopia, nausea, ataxia, and blurred vision. Rare idiosyncratic adverse effects include aplastic anemia, agranulocytosis, thrombocytopenia, and Stevens-Johnson syndrome. Asymptomatic elevation of liver enzymes is observed commonly during the course of therapy in 5-10% of patients. Rarely, severe hepatotoxic effects can occur. CBZ induces the metabolism of tricyclic antidepressants, oral contraceptives, and warfarin. Because CBZ induces its own metabolism causing an increase in clearance and a decrease in levels and effect by time !!. Phenytoin (Epanutin) A major first-line AED in the treatment of partial and secondary generalized seizures. It is not indicated for myoclonus and absence seizures. It also has an inhibiting effect on calcium channels The adverse-effect profile (e.g, gingival hyperplasia and coarsening of the facial features in women) makes its use less desirable than CBZ in some patients Osteoporosis routine screening must be performed to detect the condition early. CNS effects occur particularly in the cerebellum and the vestibular system, causing ataxia and nystagmus., Diplopia. Oxcarbazepine (Trileptal ) Oxcarbazepine (OXC) is a recently developed analogue of CBZ. It was developed in an attempt to maintain the benefits of CBZ while avoiding its auto-induction and drug interaction properties. OXC now is considered a first-line therapy in some countries. Lamotrigine (Lamictal) It has been found to inhibit depolarization of the glutaminergic presynaptic membrane, thus inhibiting release of glutamate. The most dangerous side effect is idiosyncratic adverse effects : skin rash, Stevens-Johnson syndrome. B-GABA Receptor Agonists Clonazepam (rivotril,…) Clonazepam, was one of the first benzodiazepines to be used for epilepsy. It is used in the treatment of all types of myoclonus and is useful in patients with concomitant anxiety disorder. Clonazepam has higher affinity for the GABA-A receptor site than diazepam. It may have some action on sodium-channel conductance  Phenobarbital PHB is the most prescribed AED of the 20th century. It is a very potent anticonvulsant with a broad spectrum of action. Currently, its use is limited because of its adverse effects. It has a direct action on GABA-A. It also reduces sodium conductance and calcium influx and depresses glutamate excitability. The most important adverse effects of PHB are cognitive and behavior alterations. Children are more likely than adults to exhibit behavioral changes (e.g. paradoxical hyperkinesis). Sedation is prominent, particularly at the beginning of therapy, and usually subsides, psychomotor slowing, poor concentration, depression, irritability, ataxia. C. AEDs with Potential GABA Mechanism of Action The enzyme glutamic acid decarboxylase (GAD) converts glutamate into gamma-aminobutyric acid (GABA). Currently, valproate (VPA) and gabapentin (GBP) are known to have some effect on this enzyme and thereby enhance the synthesis of GABA, Valproate (Depakine) VPA is one of the most used AEDs around the world. It is the drug of choice for primary generalized epilepsies and is also approved for the treatment of partial seizures. Excellent control in patients with newly diagnosed typical absence seizure. It is the drug of choice for juvenile myoclonic epilepsy and can be used in other types of myoclonus. In addition, it is a first-line drug in photosensitive epilepsy. It is a second choice in the treatment of infantile spasms.  Its anticonvulsant effect (Depakine) has been attributed to 1-The blockade of voltage-dependent sodium channels. 2-Increased brain levels of gamma-aminobutyric acid (GABA), possibly by inhibiting GABA degradative enzymes, such as GABA transaminase, 3- Inhibiting the re-uptake of GABA by neuronal cells. 4- Enhance the synthesis of GABA, (enhance conversion of glutamate into gamma-aminobutyric acid )  Dose-related adverse effects include nausea, vomiting tremor, sedation, confusion or irritability, and weight gain. Hair loss. VPA has adverse endocrine effects, including change in sex hormone levels causing anovulatory cycles, amenorrhea, and polycystic ovary syndrome. Bone marrow suppression with neutropenia. Acute pancreatitis is rare but potentially fatal and usually reverses after withdrawal of VPA. The most serious idiosyncratic adverse effect is hepatotoxicity. This is observed mainly in patients younger than 2 years and with polytherapy. Glutamate Blockers Glutamate and aspartate are the most two important excitatory neurotransmitters in the brain. Topiramate (Topamax) Topiramate is a very potent anticonvulsant. Topiramate has multiple mechanisms of action. It exerts an inhibitory effect on sodium conductance, enhances GABA by unknown mechanisms, inhibits glutamate receptor.  AEDs with Other Mechanisms of Action Levetiracetam (Keppra) The mechanism of action is possibly related to a brain- specific stereo-selective binding site, synaptic vesicle protein 2A (SV2A). SV2A appears to be important for the availability of calcium-dependent neurotransmitter vesicles ready to release their content. LEV inhibits Ca2+ release from the sensitive stores without reducing Ca2+ storage, which could explain some of LEV’s antiepileptic properties. Surgery Epilepsy surgery is an option for patients whose seizures remain resistant to treatment with anticonvulsant medications who also have symptomatic localization-related epilepsy; a focal abnormality that can be located and therefore removed. The evaluation for epilepsy surgery is designed to locate the "epileptic focus" (the location of the epileptic abnormality) and to determine if ressective surgery will affect normal brain function. Physicians will also confirm the diagnosis of epilepsy to make sure that spells arise from epilepsy (as opposed to non- epileptic seizures).  Surgery The evaluation typically includes neurological examination, Routine DEEG, Long-term video-DEEG monitoring, and neuroimaging such as MRI, The most common surgeries are the resection of lesions like tumors or arteriovenous malformations, which, in the process of treating the underlying lesion, often result in control of epileptic seizures caused by these lesions.  Surgery The most common form of intractable epilepsy in these disorders in adults is temporal lobe epilepsy with hippocampal sclerosis. The most common type of epilepsy surgery is the anterior temporal lobectomy, or the removal of the front portion of the temporal lobe including the amygdala and hippocampus. Some neurosurgeons recommend selective amygdala- hippocampectomy because of possible benefits in postoperative memory or language function. Vagal Nerve Stimulus(VNS)/ Pacemaker of Brain. Electrical stimulation of the vagus nerve by surgically implanting a pacemaker-like device ( vagus nerve stimulation). VNS by direct or indirect activation of vagal afferents through electrical stimulation by such device helps in refraining the episodes of seizures. VNS was found to be most effective among pediatric patients, with reduction frequency of seizures around 50–65% Differential Diagnosis of Epilepsy Summary Thank you  CMS; 511 SPINAL CORD DISORDERS Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4 ILOs Identify the anatomical structure of spinal cord. Study the different spinal cord disorders clinical presentation, investigation and treatment. Differentiate between intra-axial and extra-axial conditions. Differentiate between causes of paraplegia. Spinal cord Spinal cord is formed of 31 Segments (cervical, dorsal, lumbar, Sacral and coccygeal. From these segment spinal roots arise (1) Gracile fasciculus of Goll; (2) Cuneate fasciculus of Burdarch (dorsal column); (3) Lissauer's tract; (4) Semilunar tract (Schultz’s comma); (5)Thoracic nucleus of Clarke; (6) Intermediate column; (7) Posterior spinocerebellar tract; (8) Anterior spinocerebellar tract; (9) Lateral spinothalamic tract; (10) Anterior spinothalamic tract; (11) Spino-olivary tract; (12) Spinotectal tract; (13)Tectospinal tract; (14) Anterior corticospinal tract; (15) Reticulospinal tract; (16) Anterior vestibulospinal tract; (17) Olivo-spinal tract; (18) Anterior column (gray matter); (19) Reticular formation of the spinal cord; (20) Lateral corticospinal tract; (21) Lateral vestibulospinal tract; (22) Rubro spinal tract; Lamina of Rexed (I to X-gray matter). (B) Longitudinal axis of the spinal cord showing the cervical and lumbar enlargements and the respective transverse sections and the distance from the dura to the surface of the cord at different levels. Spinal cord disorders Spinal cord pain types Extramedullary lesion (an expanding lesion) outside the cord produces signs and symptoms from root and segmental damage. ROOT – lower motor neuron (L.M.N.) and sensory impairment appropriate to the distribution of the damaged root. SEGMENTAL (L.M.N.) and sensory impairment appropriate to segmental level. Interruption of ascending sensory and descending motor tracts produces sensory impairment and an upper motor neuron (U.M.N.) deficit below the level of the lesion. Lesions within the cord (intramedullary) produce segmental signs and symptoms.  BROWN SEQUARD SYNDROME MOTOR DEFICIT – dragging of the leg. In high cervical lesions weakness of finger and hand movements are noted on the side of the lesion. UPPER MOTOR NEURON (u.m.n.) signs (maximal on side of lesion): – weakness in a ‘pyramidal’ distribution, i.e. arms – extensors predominantly affected; legs – flexors predominantly affected. – increased tone, clonus; – increased reflexes; – extensor plantar response. SENSORY DEFICIT * numbness may occur on the same side as the lesion joint position sense and accurate touch localisation (two-point discrimination) impaired on side of lesion. * A burning dysaesthesia on the opposite side. –– Pinprick and temperature sensation impaired on opposite side. Spinal cystic lesions  SYRINGOMYELIA Syringomyelia is the acquired development of a cavity (syrinx) within the central spinal cord. The lower cervical segments are usually affected, but extension may occur upwards into the brain stem (syringobulbia) or downwards as far as the filum terminale. The cavitation appears to develop in association with obstruction: – around the foramen magnum in conjunction with the Chiari malformation. – secondarily to trauma or arachnoiditis. Clinical features – Dissociated sensory loss (i.e. loss of pain and temperature sensation with retention of other senses) occurring in a cape-like distribution. Painless burns are a classic sign. – Wasting and weakness of the small muscles of the hand and winging of the scapula from anterior horn cell involvement. Scoliosis often results. – Long tract signs follow. – Brain stem signs may appear, either from syringobulbia or an associated Chiari malformation. – Hydrocephalus occurs in 25% but is usually asymptomatic. Spinal infection ACUTE EPIDURAL ABSCESS Occurs in debilitated patients – diabetes, malignancy, liver or renal failure, intravenous drug abuse and alcoholism. Organism: Staphylococcus aureus is the most common agent (90% of cases). Spread: Haematogenous, e.g. from a boil or furuncle, or direct from vertebral osteomyelitis. Site: Usually thoracic but may affect any level and be extensive. Cord damage occurs either from direct compression or secondary to a thrombophlebitis and venous infarction. Clinical features: Develops over several days mimicking a rapidly progressive extradural tumour or haematoma with bilateral leg weakness, a sensory level and urinary retention, but distinguishing features are: – very severe pain and tenderness over the involved site. – toxaemia: pyrexia, malaise, increased pulse rate. – rigidity of neck and spinal column, with marked resistance to flexion. As the abscess extends upwards, the sensory level may rise. Investigations: Straight X-ray may or may not show an associated osteitis or discitis. An MRI or myelogram confirms the site of the extradural lesion. CSF examination, if performed shows an increased white cell count, usually polymorphonuclear, but may be normal A leucocytosis is usually present in the peripheral blood and the ESR raised. Blood cultures are often positive. Management: Urgent decompressive laminectomy and abscess drainage combined with intravenous antibiotic therapy over some weeks provide the best chance of recovery of function. In the cervical spine, anterior collections may be drained through the disc space.  Spinal tuberculosis Pott`s disease of the spine The classic systemic features of weight loss, night fever and cachexia are often absent. Pain occurs over the affected area and is made worse by weight bearing. Symptoms and signs of cord compression occur in approximately 20% of cases. The onset may be gradual as pus, caseous material or granulation tissue accumulate, or sudden as vertebral bodies collapse, and a kyphosis develops. Investigation: plain x-ray, then MRI scan of the spine. Management of TB Clinical history and bony tenderness over the affected spine are suggestive A needle biopsy is often sufficient, but occasionally an exploratory operation (costotransversectomy) is required. Long-term anti-tuberculous therapy is commenced. If signs of cord compression develop, decompression surgery is necessary Blood supply of the spinal cord Blood supply of the spinal cord Cervical arteries Intercostal artery Anterior spinal artery Artery of Adamkiewicz Sacral arteries Spinal cord infarction Anterior spinal artery syndrome The level at which infarction occurs determines symptoms and signs. Characteristic features include: – Radicular pain at onset – Sudden para/quadriplegia – Flaccid limbs days spastic – Areflexia for days then hyperreflexia and extensor plantar responses – Sensory loss to pain and temperature up to the level of cord damage – Preserved vibration and joint position sensation (dorsal columns supplied by the posterior spinal arteries) – Urinary retention Investigation – Exclude other causes of acute para/quadriplegia – cord compression, Guillain-Barré syndrome – by appropriate imaging or neurophysiology – Confirm spinal ischaemia by MRI (T2 weighted imaging showing hyperintense signal changes) – Explore possible sources of spinal ischaemia Small vessel diseases diabetes – random or fasting blood glucose - vasculitis - neurosyphilis - endarteritis secondary to – CSF meningeal infection or granulomatous disease aortic (large) vessel diseases * atheromatous – vascular risk factor e.g. cholesterol * embolic – echocardiography, blood cultures * thrombotic – coagulation screen * dissection/aneurysm – transoesophageal echo (TOE) angiography * hypotension – ECG, cardiac enzymes Treatment is symptomatic and the outcome variable.  Posterior spinal artery syndrome This is rare as white matter structures are less vulnerable to ischaemia. The dorsal columns are damaged, and ischaemia may extend into the posterior horns. Clinical features: – Loss of tendon reflexes/motor weakness – Loss of joint position sense. Venous infarction A rapid ‘total’ cord syndrome with poor outcome often associated with pelvic sepsis. Anatomy of spines In between spine bodies of vertebral column there are intervertebral discs. Intervertebral discs act as shock absorbers for the bony spine. A tough outer layer – the annulus fibrosis surrounds a softer central nucleus pulposus. Disc prolapse and spondylosis pathology Discs degenerate with age; aging The fluid within the nucleus pulposus gradually drying out; dehydration. Disc collapse produces excessive strain on the facet joints, i.e. the superior and inferior articulatory processes of each vertebral body, and leads to degeneration and hypertrophy Disc prolapse and spondylosis pathology Disc degeneration leads to a tear in the annulus fibrosis, perhaps precipitated by an injury or an excessive mechanical load. An acute disc prolapse occurs when the soft nucleus herniates through the annular tear causing irritation and/or compression of the adjacent nerve root. A ‘free fragment’ of the nucleus pulposus may extrude and lie above or below the level of the disc space. Herniation usually occurs posterolaterally, but may occasionally occur centrally, compressing the cauda equina. Lumbar disc prolapse Posterolateral disc protrusion Injury: A history of falling, or lifting heavy weights; associated back pain often precedes the onset of leg symptoms. Leg pain: Root irritation or compression produces pain in the distribution of the affected root and this should extend below the mid-calf. Coughing, sneezing or straining aggravates the leg pain which is usually more severe than any associated backache. If compression causes severe root damage the leg pain may disappear as neurological signs develop. Sensory symptoms: Numbness or paraesthesia occur in the distribution of the affected root. Central disc protrusion Symptoms and signs of central disc protrusion are usually bilateral, although one side is often worse than the other. Leg pain: Extends bilaterally down the back of the thighs. Pain may disappear with the onset of motor loss. Paraesthesia: Occurs in the same distribution. Sphincter paralysis: Loss of bladder and urethral sensation with intermittent or complete retention of urine occurs in most patients. Anal sensation is usually impaired and accompanies constipation. Investigation Management (a) Posterolateral disc protrusion CONSERVATIVE: Most bouts of leg pain settle spontaneously by taking simple measures: – Analgesics, muscle relaxants. – Avoiding heavy lifting and bending. Picking up objects from the floor, should be performed by bending the knees and keeping the back straight – Bed rest with a firm mattress, but only if pain prevents mobilisation INDICATIONS FOR OPERATION – Severe unremitting leg pain despite conservative measures. – Recurrent attacks of leg pain, especially when causing repeated time loss from work. – The development of a neurological deficit (foot drop) with unremitting pain. Management (b) Central disc protrusion Compression of the cauda equina from a central disc usually requires urgent treatment, particularly if signs and symptoms have developed within 24–48 hours. If symptoms have progressed to painless urinary retention with overflow incontinence, then the outcome is poor and the timing of surgery may not influence the results. In contrast to posterolateral protrusions, large central discs may require a one or two level laminectomy to minimise the risk of further root damage. After disc removal, recovery of function may continue for up to 2 years, but results are often disappointing. Although most regain bladder control, few have completely normal function and in many, disordered sexual function persists. CERVICAL SPONDYLOSIS The mobile cervical spine is particularly subject to osteoarthritic change and this occurs in more than half the population over 50 years of age. Approximately 20% develop symptoms. Relatively few require operative treatment. CLINICAL FEATURES Radiculopathy symptoms: Pain: a sharp stabbing pain, worse on coughing, may be superimposed on a more constant deep ache radiating over the shoulders and down the arm. Paraesthesia: Numbness or tingling follows a nerve root distribution. Root signs: – Sensory loss, i.e. pin prick deficit in the appropriate dermatomal distribution. – Muscle (L.M.N.) weakness and wasting in appropriate muscle groups, e.g. C5, C6... biceps, deltoid: C7... triceps. – Reflex impairment/loss, e.g. C5, 6... biceps, supinator jerk: C7... triceps jerk. – Trophic change: In long-standing root compression, skin becomes dry, scaly, inelastic, blue and cold. Myelopathy Arms: L.M.N. signs and symptoms, as above,at the level of the lesion and/or U.M.N. signs and symptoms below level of the lesion, e.g. C5 lesion: deltoid and biceps weakness and wasting; reduced biceps reflex; increased finger reflex. C3/4 lesions produce syndrome of numb clumsy hands (reflecting posterior column loss). Legs: U.M.N. signs and symptoms, i.e. difficulty in walking due to stiffness; ‘pyramidal’ distribution weakness, increased tone, clonus and extensor plantar responses; sensory symptoms and signs are variable and less prominent. Sphincter disturbance is seldom a prominent early feature. CERVICAL SPONDYLOSIS MANAGEMENT Conservative – Analgesics – Cervical collar Indications for operation 1. Progressive neurological deficit – myelopathy or radiculopathy. 2. Intractable pain, when this fails to respond to conservative measures. 3. acute disc protrusion. CMS; 511 HEADACHE Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4 What should you know about Headache? Definition Different disorders presented with headache Migraine headache with and without aura Other facial pain disorders Clinical approach to a patient with headache. 1) Recognize primary vs. secondary headaches 2) Recognize the prevalence and burden of headache disorders 3) Understand that headaches are specific neurologic disorders that include pain 4) Recognize frequency/prevalence of main headache types in clinic and in the community 5) Recognize symptoms of main types of headaches 6) Recognize red flags in headaches 7) Understand the workup in cases of headache 8) Understand the main lines of management (acute, preventative, lifestyle)  HEADACHE Headache is a symptom, not a disease or disorder Headache is a common symptom arising from psychological, otological, ophthalmological, neurological or systemic disease. Definition: Pain or discomfort between the orbits and occiput, arising from pain-sensitive structures. What are the Intracranial structures are: pain sensitive venous sinuses, cortical veins, basal arteries, dura of anterior, structures middle and posterior fossae. Extracranial structures are: Scalp vessels and muscles, orbital contents, mucous membranes of nasal and paranasal spaces, external and middle ear, teeth and gums.  Headache Classification Primary Headaches Secondary Heahaches Trigeminal Tumors Tension-Type Migraine Autonomic headache Sinus-related Cephalagia headache Cluster headache Cervicogenic Paroxysmal Headache Hemicrania Medication Overuse SUNCT headache (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) Hemicrania Continua Primary Headache Intrinsic dysfunction of the nervous system Most patients presenting to PCP with headache have primary headache syndromes Episodic headache: more common Chronic headache: attacks occurring more frequently than 15 days/month for more than 6 months  14 days a month) can cause medication overuse headaches(MOH). These do not respond to prophylactic agents and will improve on stopping the regular analgesics This condition can take some weeks and headaches can be worse in the short-term. Transformed migraine If patients with migraine go on to develop chronic daily headache without overusing medication It usually responds to migraine prophylactic agents.  CLUSTER HEADACHES (Histamine cephalgia or migrainous neuralgia) Cluster headaches occur less frequently than migraine, and more often in men, with onset in middle age. Characterized by episodes of severe unilateral pain, lasting 10 minutes to 2 hours, around one eye, associated with conjunctival injection, lacrimation, rhinorrhea and occasionally a transient Horner’s syndrome. The episodes occur between once and many times per day, often wakening from sleep at night. ‘Clusters’ of attacks separated by weeks or even many months. Alcohol may precipitate the attacks.’ It is a form of trigeminal autonomic cephalalgia, where there is a combination of facial pain and autonomic dysfunction. Other Trigeminal Autonomic Cephalgias Other rarer combinations of facial pain and autonomic symptoms include: Hemicrania continua: continuous unilateral moderately severe head pain with exacerbations and variable tearing and partial Horner’s syndrome. More common in women than men (3:1). Responds dramatically to indomethacin. Paroxysmal hemicrania: Same pain but lasts 2-45 minutes multiple times a day. Responds to indomethacin. Short-lasting Unilateral Neuralgiform pain with Conjunctival injection and Tearing (SUNCT): brief pain lasting seconds to 3 minutes with associations described in its name. Women : men, 2:1. Does not respond to indomethacin. Lamotrigine has some effect. Giant cell arteritis GIANT CELL (TEMPORAL) ARTERITIS An autoimmune disease of unknown cause, presents with throbbing headache in patients (males) over 60 often with general malaise and fever. The involved vessel, usually the superficial temporal artery, may be tender, thickened, and but non pulsatile. Neurological symptoms: strokes, hearing loss, myelopathy and neuropathy. Jaw claudication: pain when chewing or talking due to ischemia of the masseter muscles is pathognomonic. Visual symptoms are common with blindness (transient or permanent) or diplopia. Associated systemic symptoms – weight loss, lassitude and generalized muscle aches – polymyalgia rheumatica in one-fifth of cases. Duration: the headache is intractable, lasting until treated. Mechanism: Large and medium-sized arteries undergo intense ‘giant cell’ infiltration, with fragmentation of the lamina and narrowing of the lumen, resulting in distal ischemia as well as stimulating pain sensitive fibers. Occlusion of important end arteries, e.g. the ophthalmic artery, may result in blindness; occlusion of the basilar artery may cause brain stem or bilateral occipital infarction. GIANT CELL (TEMPORAL) ARTERITIS Diagnosis: ESR usually high. Blood film shows anemia, thrombocytosis. C-reactive protein and hepatic alkaline phosphatase elevated. Biopsy of 1 cm length of temporal artery is often diagnostic. Treatment: Urgent treatment, prednisolone 60 mg daily, prevents visual loss or brain-stem stroke, as well as relieving the headache. If complications have already occurred e.g. blindness, give parenteral high dose steroids. Monitoring the ESR allows gradual reduction in steroid dosage over several weeks to a maintenance level, e.g. 5 mg daily. Most patients eventually come off steroids; 25% require long-term treatment and if so, complications commonly occur. Secondary headache HEADACHE OF Characteristics: Generalized, aggravated by bending or RAISED coughing. INTRACRANIAL worse in the morning on awakening; may awaken patient from sleep. PRESSURE the severity of the headache gradually progresses. Associated features: vomiting in later stages. transient loss of vision (obscuration) with sudden change in posture. eventual impairment of conscious level Management: Further investigations are essential : CT or MRI  HEADACHE DUE TO INTRACRANIAL HAEMORRHAGE Characteristics: instantaneous onset. severe pain, spreading over the vertex to the occiput, or described as a ‘sudden blow to the back of the head’. patient may drop to knees or lose consciousness. Associated features: usually accompanied by vomiting. focal neurological signs suggest a hematoma (hemiplegia). Management: further investigation – CT scan Consider sudden severe headaches to be due to subarachnoid hemorrhage until proved otherwise. NON-NEUROLOGICAL CAUSES OF HEADACHE Local causes: in the head Sinuses: Well localized. Worse in morning. Affected by posture, e.g. bending. X-ray – sinus opacified. Treatment – decongestants or drainage. Ocular: Refraction errors may result in ‘muscle contraction’ headache, resolves when corrected with glasses. Acute glaucoma can produce headache but is accompanied by other symptoms, misting of vision, ‘haloes’. Dental disease: Discomfort localized to teeth. Check for malocclusion. Check temporomandibular joints. Systemic causes: Headache may accompany any febrile illness or may be the presenting feature of accelerated hypertension or metabolic disease, e.g. hypoglycemia, hypercalcemia. Many drugs produce headache through vasodilatation, e.g. bronchodilators, antihistamines Drug withdrawal, e.g. amphetamines, benzodiazepines, caffeine. Cervicogenic Headache Differentiate from migraine or other syndromes Analgesics may be tried as for migraine Reserve triptans/ergots for refractory cases Rebound often a significant issue Therapy directed at neck may help Facet blocks, trigger point injections, nerve blocks, TENS, physical therapy POST-TRAUMATIC HEADACHE A ‘common migraine’ or ‘tension-like’ headache may arise after head injury and accompany other symptoms including light- headedness, irritability, difficulty in concentration and in coping with work. This will often respond to amitriptyline or migraine prophylaxis. Clinical approach to patient with headache Full detailed history from the patient and informant Selective detection of life-threatening disorders Exclude non neurologic causes of headache Full detailed general and neurological examination Further investigation accordingly Proper treatment.  Red Flags Neurologic General Symptoms/Signs Symptoms/signs ○ Weakness/hemiparesis ○ Fever ○ Ataxia ○ Repeated vomiting ○ Diplopia ○ High blood pressure ○ Disturbed consciousness ○ Lymphadenopathy ○ Meningism Treatment of Headache Acute Preventive Simple analgesics To prevent attacks Ergots To prevent transformation to Migraine-specific (for chronic headache example, triptans) Anti-epileptics Lifestyle Anti-hypertensives Tricyclic anti-depressants Good Sleep Migraine specific (for Regular meals example, Anti-CGRP) Hydration Low caffiene Headache review cases and questions 30 years old female patient medically free, came to the clinic because of persistent pain all over her head mainly in the neck and radiating frontally, occur several hours per day and repeated more than 15 days per month, not associated with nausea or vomiting and relieved by analgesics, MRI brain and cervical spine done and were normal, the most probable diagnosis is A. Chronic migraine B. Tension type headache C. Medication over use headache D. New onset persistent daily headache female patient presented to clinic by attack of headache, throbbing in character in the left side of the head associated with photophobia and phonophobia, lasting for few hours ,this attack is preceded by visual flashes, the most suitable line of treatment during the attack:  A. indomethacin B. non-steroidal analgesics C. triptans D. antidepressants A 42y old male complaining of repeated attacks over the past month lasting for about one hour causing him severe right periorbital pain associated with lacrimation of right eye and mild ptosis, the most likely diagnosis is:  A. Cluster headache B. Migraine C. Tension headache D. Trigeminal neuralgia All the following regarding headache is true except: A. secondary headache is the most common type of headache B. migraine is more common in females C. chronic headache is considered when the attacks occurred for more than 6 months D. autonomic cephalagia is a type of primary headache Thank you  CMS; 511 CNS INFECTIONS Prof. Naglaa Elkhayat F A C U L T Y O F M E D I C I N E F A L L 2 0 2 4 ILOs Blood brain barrier (BBB) Definitions of CNS infections Causes Clinical presentations Diagnosis Treatment Introduction The CNS is the processing center of the body and consists of the brain and the spinal cord. Both are protected by three layers of membranes known as meninges, the