PHYSICIANS MEET A CASE OF SEIZURE  Prof Dr A Gowrishankar’s Unit M4 Unit,02-06-10
PATIENT PROFILE <ul><li>Mr Sigamani , 38 yrs of age </li></ul><ul><li>Non smoker, non alcoholic </li></ul><ul><li>Diabetic...
<ul><li>No h/o fever, blurring of vision </li></ul><ul><li>No h/o trauma </li></ul><ul><li>No h/o hypertension, CAD, PTB <...
<ul><li>On Examination </li></ul><ul><li>Patient was drowsy, confused, disoriented </li></ul><ul><li>Afebrile </li></ul><u...
<ul><li>System examination: </li></ul><ul><li>CVS,RS,Abd : normal </li></ul><ul><li>Neurologic Ex: drowsy, confused. </li>...
<ul><li>Treated with 25%dextrose( suspected hypoglycemia), </li></ul><ul><li>Nasal oxygen  </li></ul><ul><li>IVFluids </li...
INVESTIGATIONS <ul><li>Hb: 13 g% </li></ul><ul><li>TC: 6100, DC : P50L48E2 </li></ul><ul><li>ESR 6/14 </li></ul><ul><li>PC...
 
<ul><li>T  Aspirin  150 mg OD and </li></ul><ul><li>T  Atorvastatin  20mg HS were added. </li></ul><ul><li>Patient recover...
 
 
<ul><li>An urgent MRI was taken which showed  venous infarct in the left frontal lobe with superior sagittal and superfici...
 
<ul><li>Patient was started on  heparin 5000U IV TDS </li></ul><ul><li>Inspite of AEDs pt had focal seizures with secondar...
<ul><li>Patient recovered over the next couple of days </li></ul><ul><li>Seizures seized, CN palsies significantly improve...
<ul><li>Insulin regime </li></ul><ul><li>HA 6-6-6 raised upto 12-12-12 premeal. </li></ul><ul><li>HM 6-0-4 raised upto 20-...
FURTHER INVESTIGATIONS… <ul><li>Cardiac status was normal and ECHO showed no RWMA, normal LV function </li></ul><ul><li>Ca...
THROMBOPHILIA PROFILE <ul><li>Protein C  184% ( 70-140) </li></ul><ul><li>Protein S  158% (60-150) </li></ul><ul><li>S Hom...
FINAL DIAGNOSIS <ul><li>Type 2 Diabetes Mellitus </li></ul><ul><li>Dyslipidemia </li></ul><ul><li>Cortical Venous Thrombos...
CORTICAL VENOUS THROMBOSIS <ul><li>Incidence:  5/million  in an year </li></ul><ul><li>Accounts for  0.5% of all strokes <...
CAUSES OF VENOUS THROMBOSIS <ul><li>INHERITED THROMBOPHILIA  </li></ul><ul><ul><li>Factor V Leiden mutation  </li></ul></u...
<ul><li>44% - had more than one cause or predisposing factor, and  </li></ul><ul><li>22% - Congenital/genetic thrombophili...
CVT-CLINICAL ASPECTS <ul><li>The most common symptoms and signs are </li></ul><ul><ul><ul><li>Headache  </li></ul></ul></u...
PRESENTING SYMPTOMS OF CVT <ul><li>COMMON SYMPTOMS </li></ul><ul><li>Isolated intracranial hypertension </li></ul><ul><li>...
<ul><li>ISOLATED HEAD ACHE </li></ul><ul><li>Headache in the absence of intracranial hypertension, subarachnoid haemorrhag...
DIAGNOSIS <ul><li>Neuroimaging of the thrombosed vessel </li></ul><ul><li>The current gold standard is MRI with MRV </li><...
<ul><li>T2* SWI </li></ul><ul><li>DIFFUSION WEIGHTED IMAGES </li></ul><ul><li>For  imaging of parenchymal lesions </li></u...
<ul><li>ROLE OF D-DIMER ASSAY </li></ul><ul><li>If high index of suspicion… a D-dimer assay is more of negative predictive...
PROGNOSIS <ul><li>Very good compared to arterial events </li></ul><ul><li>15% overall death/ dependancy </li></ul><ul><li>...
<ul><li>Causes of acute death </li></ul><ul><li>TRANSTENTORIAL HERNIATION,  secondary to a large  haemorrhagic lesion  </l...
TREATMENT <ul><li>ANTITHROMBOTIC TREATMENT </li></ul><ul><li>Acute   phase ( No contraindication for anticoagulation) </li...
<ul><li>SYMPTOMATIC TREATMENT </li></ul><ul><li>Antiepileptics </li></ul><ul><li>Acute phase </li></ul><ul><li>Prevention ...
HOMOCYSTEINE and its ROLE IN CVT <ul><li>An intermediary amino acid </li></ul><ul><li>Marked elevation may be seen with  H...
HOMOCYSTEINE METABOLISM
ETIOLOGY OF HYPERHOMOCYSTEINEMIA <ul><li>Genetic defects  in the enzymes involved in homocysteine metabolism(MTHFR mutatio...
ATHEROTHROMBOTIC PROPERTIES OF HOMOCYSTEINE <ul><li>Homocysteine has primary atherogenic and prothrombotic properties.  </...
<ul><li>Moderate  (15 to 30 µmol/L)  </li></ul><ul><li>Intermediate  (30 to 100 µmol/L)  </li></ul><ul><li>Severe  (>100 µ...
<ul><li>OTHER ASSOCIATIONS </li></ul><ul><ul><li>Venous thromboembolism </li></ul></ul><ul><ul><li>Obstetric complications...
TREATMENT <ul><li>Correcting nutritional inadequacy of folic acid, vitamin B12, and choline (betaine) will lower homocyste...
CORTICAL VENOUS THROMBOSIS <ul><li>CVT needs  high index of suspicion  for diagnosis because of wide spectrum of symptoms ...
HYPERHOMOCYSTEINEMIA <ul><li>Can be inherited/ acquired </li></ul><ul><li>Severest form is  homocystinuria  ( CBS deficien...
DIABETES AND CVT <ul><li>Neurologic symptoms in DKA are quiet common due to cerebral edema, but reports say CVT could be a...
 
REFERENCES <ul><li>UpToDate 17.3 </li></ul><ul><li>Cerebral venous thrombosis: an update </li></ul><ul><li>Marie-Germaine ...
 
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A Case of Cortical Venous Thrombosis

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A Case of Cortical Venous Thrombosis

  1. 1. PHYSICIANS MEET A CASE OF SEIZURE Prof Dr A Gowrishankar’s Unit M4 Unit,02-06-10
  2. 2. PATIENT PROFILE <ul><li>Mr Sigamani , 38 yrs of age </li></ul><ul><li>Non smoker, non alcoholic </li></ul><ul><li>Diabetic for 3 yrs on OHA </li></ul><ul><li>Presented with seizures for last 2 days </li></ul><ul><li>First episode lasted about 5 minutes, GTCS with h/o post ictal confusion and transient LOC, regained consciousnes with no residual neurologic deficits. </li></ul><ul><li>Subsequently he had 4 episodes on the day of admission, GTCS ,each lasting 5-10 minutes, lost consciousness </li></ul><ul><li>H/o severe throbbing head ache + </li></ul><ul><li>H/o vomiting +, non projectile, non bilious </li></ul>
  3. 3. <ul><li>No h/o fever, blurring of vision </li></ul><ul><li>No h/o trauma </li></ul><ul><li>No h/o hypertension, CAD, PTB </li></ul><ul><li>Not a known epileptic </li></ul><ul><li>Patient denied high risk behaviours </li></ul><ul><li>Normally born of non-consanguinous marriage </li></ul>
  4. 4. <ul><li>On Examination </li></ul><ul><li>Patient was drowsy, confused, disoriented </li></ul><ul><li>Afebrile </li></ul><ul><li>Moderately built and nourished </li></ul><ul><li>Not pale, anicteric, not cyanosed,no clubbing , no lymphadenopathy, thyroid appered normal,no pedal edema </li></ul><ul><li>Vitals were stable (PR 82/min,BP 120/86 mm Hg) </li></ul>
  5. 5. <ul><li>System examination: </li></ul><ul><li>CVS,RS,Abd : normal </li></ul><ul><li>Neurologic Ex: drowsy, confused. </li></ul><ul><li>Moves all 4 limbs </li></ul><ul><li>No cranial nerve deficits. </li></ul><ul><li>Pupils bilaterally 2mm, reacting </li></ul><ul><li>No involuntary movements </li></ul><ul><li>No meningeal signs. </li></ul><ul><li>DTR normal </li></ul><ul><li>Plantar b/l ↓ </li></ul><ul><li>Fundus: papilledema present </li></ul>
  6. 6. <ul><li>Treated with 25%dextrose( suspected hypoglycemia), </li></ul><ul><li>Nasal oxygen </li></ul><ul><li>IVFluids </li></ul><ul><li>Inj.Phenytoin 15-20 mg/kg Loading dose </li></ul><ul><li>Inj Mannitol 175 ml IV BD </li></ul><ul><li>Inj Ranitidine 50mg IV BD </li></ul><ul><li>Inj Cefotaxime 1g IV BD </li></ul><ul><li>Inj Diazepam slow iv sos </li></ul>
  7. 7. INVESTIGATIONS <ul><li>Hb: 13 g% </li></ul><ul><li>TC: 6100, DC : P50L48E2 </li></ul><ul><li>ESR 6/14 </li></ul><ul><li>PCV 39% </li></ul><ul><li>RBS- 186 </li></ul><ul><li>BU- 22 </li></ul><ul><li>S Cr- 0.9 </li></ul><ul><li>SE Na 133/ K: 3.9 </li></ul><ul><li>Urine R/E sugar ++ , </li></ul><ul><li>albumin- nil, </li></ul><ul><li>1-2 pc/hpf </li></ul><ul><li>ECG: normal </li></ul><ul><li>CXR: normal </li></ul><ul><li>CT Brain : Hypodensity noted in left parietal region </li></ul><ul><li>Urine ketones: negative </li></ul><ul><li>FLP: TC 226 </li></ul><ul><li>TG 222 </li></ul><ul><li>HDL 50 </li></ul><ul><li>LDL 132 </li></ul><ul><li>VLDL 44 </li></ul><ul><li>Ultrasound Abd: Fatty liver </li></ul>
  8. 9. <ul><li>T Aspirin 150 mg OD and </li></ul><ul><li>T Atorvastatin 20mg HS were added. </li></ul><ul><li>Patient recovered from post ictal state during first 24 hrs </li></ul><ul><li>He was persistently complaining of head ache , severe enough to disturb even during sleep. </li></ul><ul><li>On day 4 patient developed focal seizures involving his left upper limb . </li></ul><ul><li>Seizure was not getting controlled with AED( phenytoin, carbamazepine, and diazepam during ictal periods) </li></ul><ul><li>Patient continued to have seizures for the next 2 days. </li></ul><ul><li>On 7 th day of admission patient developed multiple cranial nerve palsies, on left side, VI, VII, IX, X and XII CN were involved. </li></ul><ul><li>He also developed “left hemiparesis” </li></ul>
  9. 12. <ul><li>An urgent MRI was taken which showed venous infarct in the left frontal lobe with superior sagittal and superficial sinus thrombosis . </li></ul>
  10. 14. <ul><li>Patient was started on heparin 5000U IV TDS </li></ul><ul><li>Inspite of AEDs pt had focal seizures with secondary generalistion. </li></ul><ul><li>Patient had to be shifted to IMCU and was sedated, intubated and ventilated in view of protecting airway. </li></ul>
  11. 15. <ul><li>Patient recovered over the next couple of days </li></ul><ul><li>Seizures seized, CN palsies significantly improved, with mild hemiparesis </li></ul><ul><li>Patient was shifted back to ward on day 12 </li></ul><ul><li>The seizure episodes continued for another 6 days but episodes were less frequent and less severe, with occassional worsening of cranial nerve symptoms and hemiparesis. </li></ul><ul><li>On 32 nd day when patient was discharged he had residual XII CN palsy with mild hemiparesis. </li></ul><ul><li>Patient was on acitrom 3mg OD with target INR between 2-3, to be continued for 6 months, along with physiotherapy and strict glycemic control . </li></ul>
  12. 16. <ul><li>Insulin regime </li></ul><ul><li>HA 6-6-6 raised upto 12-12-12 premeal. </li></ul><ul><li>HM 6-0-4 raised upto 20-0-10 </li></ul>Date 1/4 2/4 4/4 5/4 6/4 14/4 21/4 24/4 27/4 28/4 30/4 FBS 186 232 226 231 200 183 - - 104 82 119 PPBS (RBS) 254 367 265 - 170 380 156 124 138 -
  13. 17. FURTHER INVESTIGATIONS… <ul><li>Cardiac status was normal and ECHO showed no RWMA, normal LV function </li></ul><ul><li>Carotid doppler was normal . </li></ul><ul><li>EEG: B/L potential epileptiform pattern </li></ul><ul><li>Ophthalmologic evaluation: media clear, fundus-Papilloedema present </li></ul><ul><li>Mantoux done was negative </li></ul><ul><li>HIV: negative </li></ul><ul><li>HBsAg: Negative </li></ul>
  14. 18. THROMBOPHILIA PROFILE <ul><li>Protein C 184% ( 70-140) </li></ul><ul><li>Protein S 158% (60-150) </li></ul><ul><li>S Homocysteine: 34.43 ↑ (5.9-16) </li></ul><ul><li>Anti Cardiolipin IgG 1.27 (<10) </li></ul><ul><li>Anti Cardiolipin IgM 1.6 (<7) </li></ul><ul><li>Lupus anticoagulant: Negative </li></ul><ul><li>Serum Fibrinogen: 382 mg/dL (180-350) </li></ul><ul><li>ANA : negative </li></ul><ul><li>RA Factor: negative </li></ul><ul><li>CRP : 24 mg/L ↑ (<6mg/L) </li></ul>
  15. 19. FINAL DIAGNOSIS <ul><li>Type 2 Diabetes Mellitus </li></ul><ul><li>Dyslipidemia </li></ul><ul><li>Cortical Venous Thrombosis </li></ul><ul><li>Hyperhomocysteinemia </li></ul>
  16. 20. CORTICAL VENOUS THROMBOSIS <ul><li>Incidence: 5/million in an year </li></ul><ul><li>Accounts for 0.5% of all strokes </li></ul><ul><li>Advances in neuroimaging has allowed early diagnosis and treatment and better understanding of the evolution of the disease </li></ul><ul><li>It reduced the mortality rate from 20-30% to well below 10% </li></ul><ul><li>However diagnosis is still overlooked or delayed because of the remarkable diversity of its clinical symptoms, modes of onset, and neuroimaging signs; </li></ul><ul><li>A cause cannot be found in about 15% of cases </li></ul><ul><li>The disorder may occasionally worsen despite anticoagulation </li></ul><ul><li>CVT thus remains a diagnostic and therapeutic challenge </li></ul>
  17. 21. CAUSES OF VENOUS THROMBOSIS <ul><li>INHERITED THROMBOPHILIA </li></ul><ul><ul><li>Factor V Leiden mutation </li></ul></ul><ul><ul><li>Prothrombin gene mutation </li></ul></ul><ul><ul><li>Protein S deficiency </li></ul></ul><ul><ul><li>Protein C deficiency </li></ul></ul><ul><ul><li>Antithrombin (AT) deficiency </li></ul></ul><ul><ul><li>Homocysteinemia </li></ul></ul><ul><ul><li>Rare disorders </li></ul></ul><ul><ul><li>Dysfibrinogenemia </li></ul></ul><ul><li>ACQUIRED DISORDERS </li></ul><ul><ul><li>Malignancy </li></ul></ul><ul><ul><li>Presence of a central venous catheter </li></ul></ul><ul><ul><li>Surgery, especially orthopedic </li></ul></ul><ul><ul><li>Trauma </li></ul></ul><ul><ul><li>Pregnancy </li></ul></ul><ul><ul><li>Oral contraceptives </li></ul></ul><ul><li>Hormone replacement therapy </li></ul><ul><li>Tamoxifen, Bevacizumab, </li></ul><ul><ul><li>Thalidomide, Lenalidomide </li></ul></ul><ul><li>Immobilization </li></ul><ul><li>Congestive failure </li></ul><ul><li>Antiphospholipid antibody syndrome </li></ul><ul><li>Myeloproliferative disorders </li></ul><ul><ul><li>Polycythemia vera </li></ul></ul><ul><ul><li>Essential thrombocythemia </li></ul></ul><ul><li>Paroxysmal nocturnal hemoglobinuria </li></ul><ul><li>Inflammatory bowel disease </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Hyperviscosity </li></ul><ul><ul><li>Waldenstrom's macroglobulinemia </li></ul></ul><ul><ul><li>Multiple myeloma </li></ul></ul><ul><li>Marked leukocytosis in acute leukemia </li></ul><ul><li>Sickle cell anemia </li></ul><ul><li>HIV/AIDS </li></ul>
  18. 22. <ul><li>44% - had more than one cause or predisposing factor, and </li></ul><ul><li>22% - Congenital/genetic thrombophilia </li></ul><ul><li>15% - No cause could be found </li></ul><ul><li>RECENT STUDIES EMPHASISE the role of hyperhomocystenaemia </li></ul><ul><li>Spontaneous intracranial hypotension </li></ul><ul><li>Thalidomide used in a patient with multiple myeloma </li></ul><ul><li>Cushing’s syndrome </li></ul><ul><li>Erythropoietin </li></ul><ul><li>High altitude as reported in the Himalayas </li></ul><ul><li>Phytoestrogens and </li></ul><ul><li>Shiatsu massage (an oriental technique of neck massage) </li></ul>
  19. 23. CVT-CLINICAL ASPECTS <ul><li>The most common symptoms and signs are </li></ul><ul><ul><ul><li>Headache </li></ul></ul></ul><ul><ul><ul><li>Seizures </li></ul></ul></ul><ul><ul><ul><li>Focal neurological deficits </li></ul></ul></ul><ul><ul><ul><li>Altered consciousness and </li></ul></ul></ul><ul><ul><ul><li>Papilloedema </li></ul></ul></ul><ul><li>Four main patterns have been identified </li></ul><ul><ul><ul><li>Isolated intracranial hypertension </li></ul></ul></ul><ul><ul><ul><li>Focal syndrome </li></ul></ul></ul><ul><ul><ul><li>Cavernous sinus syndrome and </li></ul></ul></ul><ul><ul><ul><li>Subacute encephalopathy </li></ul></ul></ul>
  20. 24. PRESENTING SYMPTOMS OF CVT <ul><li>COMMON SYMPTOMS </li></ul><ul><li>Isolated intracranial hypertension </li></ul><ul><li>Focal syndrome (deficit and/or seizure) </li></ul><ul><li>Diffuse encephalopathy </li></ul><ul><li>Any combination of the above </li></ul><ul><li>RARE SYMPTOMS </li></ul><ul><li>Cavernous sinus syndrome </li></ul><ul><li>Subarachnoid haemorrhage </li></ul><ul><li>Thunderclap headache </li></ul><ul><li>Attacks of migraine with aura </li></ul><ul><li>Isolated headache </li></ul><ul><li>Transient ischaemic attacks </li></ul><ul><li>Tinnitus </li></ul><ul><li>Isolated psychiatric symptoms </li></ul><ul><li>Isolated or multiple cranial nerve palsies </li></ul><ul><li>Clinical presentation of CVT is affected by </li></ul><ul><li>Age ofpatient, </li></ul><ul><li>Time between onset and admission to hospital, </li></ul><ul><li>Location of CVT, and </li></ul><ul><li>The presence of parenchymal lesions. </li></ul><ul><li>Patients with chronic course or delayed clinical presentation may show papilloedema on fundoscopy but this finding is less common in acute cases </li></ul>
  21. 25. <ul><li>ISOLATED HEAD ACHE </li></ul><ul><li>Headache in the absence of intracranial hypertension, subarachnoid haemorrhage, or meningitis. </li></ul><ul><li>Such cases are essentially associated with LATERAL SINUS THROMBOSIS , which should not be mistaken for lateral sinus hypoplasia. </li></ul><ul><li>The exact mechanism of the headache remains unknown </li></ul><ul><ul><li>Stretching of nerve fibres in the walls of the occluded sinus </li></ul></ul><ul><ul><li>A local inflammatory reaction </li></ul></ul><ul><li>MRI: contrast enhancement of the sinus wall surrounding the clot- the “ empty delta sign ”. </li></ul>
  22. 26. DIAGNOSIS <ul><li>Neuroimaging of the thrombosed vessel </li></ul><ul><li>The current gold standard is MRI with MRV </li></ul><ul><li>( MRI to visualise the thrombosed vessel and MRV to detect the non-visualisation of the same vessel) </li></ul><ul><li>MRI alone is limited by flow artifacts that can lead to false positives and the absence of hyperintense signal on T1 and T2-weighted images at the onset of acute thrombosis. </li></ul><ul><li>During the first 3–5 days the thrombosed sinus is isointense on T1 and hypointense on T2, and thus very difficult to differentiate from normal veins. </li></ul><ul><li>MRV alone- difficult to differentiate between thrombus or sinus hypoplasia </li></ul><ul><li>Echoplanar Susceptibility-weighted images (T2*): </li></ul><ul><li>More sensitive than T2WI especially within 3 days of onset </li></ul>
  23. 27. <ul><li>T2* SWI </li></ul><ul><li>DIFFUSION WEIGHTED IMAGES </li></ul><ul><li>For imaging of parenchymal lesions </li></ul><ul><li>It helps to differentiate </li></ul><ul><li>Vasogenic edema (↑app. DC) </li></ul><ul><li>Cytotoxic edema (↓app. DC) </li></ul>
  24. 28. <ul><li>ROLE OF D-DIMER ASSAY </li></ul><ul><li>If high index of suspicion… a D-dimer assay is more of negative predictive value(<500 ng/mL) </li></ul><ul><li>But in those patients with isolated head ache with MRI evidence of CVT, 26% had normal D-dimer </li></ul>
  25. 29. PROGNOSIS <ul><li>Very good compared to arterial events </li></ul><ul><li>15% overall death/ dependancy </li></ul><ul><li>Poor prognosistic factors </li></ul><ul><ul><ul><ul><li>CNS infection </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Any type of cancer </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Deep venous system thrombosis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Intracranial haemorrhage </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Mental status disorder </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Age>37 years </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Male gender </li></ul></ul></ul></ul>
  26. 30. <ul><li>Causes of acute death </li></ul><ul><li>TRANSTENTORIAL HERNIATION, secondary to a large haemorrhagic lesion </li></ul><ul><li>MULTIPLE LESIONS </li></ul><ul><li>DIFFUSE BRAIN OEDEMA </li></ul><ul><li>STATUS EPILEPTICUS </li></ul><ul><li>PULMONARY EMBOLISM </li></ul><ul><li>Deterioration after admission occurs in about 23% of patients, with worsening of mental status, headache, or focal deficits, or with new symptoms such as seizures. </li></ul>
  27. 31. TREATMENT <ul><li>ANTITHROMBOTIC TREATMENT </li></ul><ul><li>Acute phase ( No contraindication for anticoagulation) </li></ul><ul><li>LMWH 1mg/kg BW s/c </li></ul><ul><li>Heparin in full therapeutic dosage or APPT (2 times above normal) </li></ul><ul><li>Local intravenous thrombolysis* </li></ul><ul><li>Mechanical thrombectomy * </li></ul><ul><li>Prevention of recurrent thrombotic events with oral anticoagulants </li></ul><ul><li>CVT related to a transient risk factor, 3–6months </li></ul><ul><li>Idiopathic CVT or related to mild hereditary thrombophilia, 6–12 months </li></ul><ul><li>Recurrent CVT or severe hereditary thrombophilia, indefinite </li></ul>
  28. 32. <ul><li>SYMPTOMATIC TREATMENT </li></ul><ul><li>Antiepileptics </li></ul><ul><li>Acute phase </li></ul><ul><li>Prevention of seizures after the acute phase </li></ul><ul><ul><li>Patients with focal haemorrhagic lesions* </li></ul></ul><ul><li>Treatment of intracranial hypertension </li></ul><ul><li>Acetazolamide </li></ul><ul><li>Osmotic therapy </li></ul><ul><li>Lumbar puncture (if no parenchymal lesions) </li></ul><ul><li>Sedation and hyperventilation </li></ul><ul><li>SURGICAL PROCEDURES (lumboperitoneal shunt,ventriculoperitoneal shunt, optic nerve fenestration) </li></ul><ul><li>or Hemicraniectomy* </li></ul><ul><li>Impairment of consciousness / herniation / threatened vision </li></ul>
  29. 33. HOMOCYSTEINE and its ROLE IN CVT <ul><li>An intermediary amino acid </li></ul><ul><li>Marked elevation may be seen with Homocystinuria , an inborn error of metabolism, with typical phenotype and premature atherosclerosis </li></ul><ul><li>Due to cystathionine- β -synthase deficiency </li></ul><ul><li>AR inhertance </li></ul><ul><li>Less marked elevations: proven risk factors for cardiovascular and venous thrombotic events </li></ul><ul><li>Normal levels 5-15 μ mol/L </li></ul>
  30. 34. HOMOCYSTEINE METABOLISM
  31. 35. ETIOLOGY OF HYPERHOMOCYSTEINEMIA <ul><li>Genetic defects in the enzymes involved in homocysteine metabolism(MTHFR mutation) </li></ul><ul><li>Nutritional deficiencies in vitamin cofactors </li></ul><ul><li>Other factors including some chronic medical conditions and drugs ( fibrates, nicotinic acid, CKD - ↓removal, impaired metabolism) </li></ul><ul><li>Smoking </li></ul>
  32. 36. ATHEROTHROMBOTIC PROPERTIES OF HOMOCYSTEINE <ul><li>Homocysteine has primary atherogenic and prothrombotic properties. </li></ul><ul><li>Histopathologic hallmarks of homocysteine-induced vascular injury include </li></ul><ul><ul><li>Intimal thickening, </li></ul></ul><ul><ul><li>Elastic lamina disruption, </li></ul></ul><ul><ul><li>Smooth muscle hypertrophy, </li></ul></ul><ul><ul><li>Marked platelet accumulation, and </li></ul></ul><ul><ul><li>Formation of platelet-enriched occlusive thrombi </li></ul></ul>
  33. 37. <ul><li>Moderate (15 to 30 µmol/L) </li></ul><ul><li>Intermediate (30 to 100 µmol/L) </li></ul><ul><li>Severe (>100 µmol/L) </li></ul><ul><li>METHIONINE CHALLENGE TEST </li></ul><ul><li>IMPLICATIONS : </li></ul><ul><ul><li>Myocardial infarction, other acute coronary syndromes, and recurrent coronary events </li></ul></ul><ul><ul><li>Premature coronary heart disease </li></ul></ul><ul><ul><li>Cardiovascular and total mortality </li></ul></ul><ul><ul><li>Adverse outcomes after angioplasty </li></ul></ul><ul><ul><li>Carotid artery stenosis, Stroke , recurrent stroke , and silent brain infarct </li></ul></ul>
  34. 38. <ul><li>OTHER ASSOCIATIONS </li></ul><ul><ul><li>Venous thromboembolism </li></ul></ul><ul><ul><li>Obstetric complications </li></ul></ul><ul><ul><li>Birth defects </li></ul></ul><ul><ul><li>Osteoporosis </li></ul></ul><ul><ul><li>Dementia </li></ul></ul>
  35. 39. TREATMENT <ul><li>Correcting nutritional inadequacy of folic acid, vitamin B12, and choline (betaine) will lower homocysteine levels </li></ul><ul><li>A diet rich in fruits, vegetables, and low-fat dairy products, and low in saturated and total fat also can lower fasting serum homocysteine </li></ul><ul><li>folic acid (1 mg/day) </li></ul><ul><li>vitamin B6 (10 mg/day) </li></ul><ul><li>vitamin B12 (0.4 mg/day) </li></ul><ul><li>Normalization in two weeks </li></ul><ul><li>↑ folic acid 5 mg/day as needed (<15 µmol/L) </li></ul><ul><li>a homocysteine level >30 µmol/L or CKD the initial dose of folic acid is 5 mg/day </li></ul><ul><li>Not recommended for secondary prevention </li></ul><ul><li>Genetic testing is available </li></ul>
  36. 40. CORTICAL VENOUS THROMBOSIS <ul><li>CVT needs high index of suspicion for diagnosis because of wide spectrum of symptoms and varying signs </li></ul><ul><li>Very good prognosis and mortality only <10% with prompt treatment, near complete recovery in majority </li></ul><ul><li>Inherited(22%) and acquired thrombophilia to be screened </li></ul><ul><li>15% have no etiologic factors </li></ul><ul><li>In 44% cases >1 etiologic factors present </li></ul><ul><li>MRI with MRV is the gold std for diagnosis </li></ul><ul><li>Role of hyperhomocysteinemia on the rise </li></ul><ul><li>Anticoagulation is mainstay of treatment(IV foll. by oral) </li></ul><ul><li>Worsening if present even with treatment, surgical intervention may be needed </li></ul>
  37. 41. HYPERHOMOCYSTEINEMIA <ul><li>Can be inherited/ acquired </li></ul><ul><li>Severest form is homocystinuria ( CBS deficiency ), AR inheritance </li></ul><ul><li>MC inherited form is MTHFR mutation(thermolabile) </li></ul><ul><li>Normal level is 5-15 μ mol/L </li></ul><ul><li>Folic acid, B6, B12 deficiency causes acquired disease </li></ul><ul><li>Screening to be done in case of atherosclerosis and thrombophilia including CVT </li></ul><ul><li>Treatment is replacement of vitamins </li></ul><ul><li>Secondary prophylaxis not recommended </li></ul>
  38. 42. DIABETES AND CVT <ul><li>Neurologic symptoms in DKA are quiet common due to cerebral edema, but reports say CVT could be associated, be suspicious if patient is not responding ( dehydration and sepsis could be the precipitating factors ) </li></ul><ul><li>coagulation abnormalities such as </li></ul><ul><ul><li>decreased protein C concentration, </li></ul></ul><ul><ul><li>enhanced anticoagulation response to act. Pr. C </li></ul></ul><ul><ul><li>activated protein C resistance </li></ul></ul><ul><li>Isolated case reports of CVT (Atleast3) as the presenting symptom in type 1 diabetes with DKA are there in literature </li></ul>
  39. 44. REFERENCES <ul><li>UpToDate 17.3 </li></ul><ul><li>Cerebral venous thrombosis: an update </li></ul><ul><li>Marie-Germaine Bousser, José M Ferro </li></ul><ul><li>Lancet Neurol 2007; 6: 162–70 </li></ul><ul><li>HYPERHOMOCYSTEINEMIA AND CEREBRALVENOUS SINUS THROMBOSIS </li></ul><ul><li>Mughis Sheerani and Bhojo A. Khealani </li></ul><ul><li>Section of Neurology, Aga Khan University Hospital, Karachi, Pakistan </li></ul><ul><li>Pak J Neurol Sci 2006; 1(3):136-7 </li></ul><ul><li>Hyperhomocysteinemia in cerebral vein thrombosis </li></ul><ul><li>Ida Martinelli, Tullia Battaglioli, Paola Pedotti, Marco Cattaneo, and Pier M. Mannucci </li></ul><ul><li>Diabetic ketoacidosis presenting as a cerebral venous sinus thrombosis </li></ul><ul><li>Kristel DE KEYZER1, Koen PAEMELEIRE1, Matti DE CLERCK2, Dirk PEETERS2 and Jacques L. DE REUCK1 </li></ul><ul><li>1Department of Neurology, Ghent University Hospital, Ghent and 2Department of Neurology, AZ Groeninge, Kortrijk, Belgium </li></ul><ul><li>Recurrent Cerebral Venous Thrombosis Associated with Elevated Factor VIII </li></ul><ul><li>Mi Jung Kim, M.D., A-Hyun Cho, M.D., Young-Joo No, M.D., Hee-Young Kim, M.D., </li></ul><ul><li>Jong S. Kim, M.D. </li></ul><ul><li>Department of Neurology, University of Ulsan College of Medicine, Asan Medical Center </li></ul><ul><li>Cerebral venous thrombosis during diabetic ketoacidosis </li></ul><ul><li>S Keane, A Gallagher, S Ackroyd, M A McShane, J A Edge </li></ul><ul><li>Arch Dis Child 2002;86:204–206 </li></ul>

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