neurological manifestations of hematological disorders
TRANSCRIPT
![Page 1: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/1.jpg)
Neurological Manifestations of Hematological Disorders
DR Bipin Bhimani DM ( Neurology)(NIMHANS)
Well Care Hospital Rajkot
![Page 2: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/2.jpg)
4 Situations
• Scenario 1:
• Known case of hematological disorder leading to neurological problem
• Eg :k/c/o sickle Cell Anemia gets ischemic stroke
![Page 3: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/3.jpg)
Scenario 2
• Neurological problem as a first presenting symptom of a hidden hematological disorder
Eg:Young patient with Cerebra Venous Thrombosis gets diagnosed to have Protein C deficiency.
![Page 4: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/4.jpg)
Scenario 3
• A multisystem disorder affecting both hemato and neuro system
• Eg:A lady with psychosis and thrombocytopenia , turn outs to have SLE
![Page 5: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/5.jpg)
Scenario 4
• Neurological side effect of a drug used for hematological disorder
• Eg: Vincristine induced polyneuropathy
• Eg: 5 F-U causing Toxic leukoencephalopathy
![Page 6: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/6.jpg)
Case 1
• Boy with limping gait
• Orthopedic opinion: Normal xrays, CRP, ASO, RA
• Neuro opinion: Hemogram
![Page 7: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/7.jpg)
• Leukemia with blast crisis ( leading to joint pain )
![Page 8: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/8.jpg)
Case 2:
• Man with headache , early papilloedema • Normal CT and limited MR brain
• High MCV
![Page 9: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/9.jpg)
• Cerebral Venous sinus thrombosis on MR venogram ( due to high Homocysteine /Low B12 )
![Page 10: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/10.jpg)
Case 3:
• Patient with fluctuating symptoms ? Seizures, TIAs, and behavioral changes
• Near normal MR brain
• Blood Ix: Thrombocytopenia
![Page 11: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/11.jpg)
• TTP ( Thrombotic thrombocytopenic Purpura)
![Page 12: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/12.jpg)
Case 4:
• Girl with bilateral watershed infarcts
• ( No hypotension, normal carotid doppler, MRAngio brain, 2 D Echo )
![Page 13: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/13.jpg)
![Page 14: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/14.jpg)
![Page 15: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/15.jpg)
![Page 16: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/16.jpg)
• Idiopathic hypereosinophilia syndrome with neurotoxicity
![Page 17: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/17.jpg)
Case 5:
• Thallasemic girl with paraplegia
![Page 18: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/18.jpg)
![Page 19: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/19.jpg)
![Page 20: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/20.jpg)
![Page 21: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/21.jpg)
• Extramedullary hematopoesis in spinal canal, compressing spinal cord
![Page 22: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/22.jpg)
Hypercoaguble disorders and ischemic stroke
• Pump ( heart)• Pipe ( artery) • Passage ( blood)
![Page 23: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/23.jpg)
Hypercoagubility and ischemic stroke
• Cerebral Venous sinus thrombosis• About 8% of all ischemic strokes • Recurrent strokes • Stroke in young ( < 40), unidentified etiology • Strong family history of non – atheromatous
stroke• “cryptogenic “ ischemic strokes • paradoxical embolus through PFO
![Page 24: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/24.jpg)
Primary/inherited Hypercoaguble states
• Factor V leiden mutation/Activated protein C resistance
• Prothombin gene 20210A mutation• Protein S deficiency• Protein C deficiency• Antithrombin III deficiency • MTHFR gene mutation • Others
![Page 25: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/25.jpg)
Secondary/aquired hypercoaguable states
• APLA syndrome • Polycythemia rubra vera• Essential thrombocythemia • Myeloproliferative disorders• Sickle cell disease, hemoglobinopathies• Paraproteinemia • Iron deficiency Anemia • TTP • Hyperhomocystinemia • Pregnancy,OC Pills, DM,cancer,DIC,Ovarian Hyperstimulation
Syndrome
![Page 26: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/26.jpg)
Thrombophilia work up ( Basic)
• Hemogram• PT, aPTT• Homocystiene• ANA, VDRL• LA, ACLA • APLA • Anti-Thrombin III level• Pro Ce globe
![Page 27: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/27.jpg)
Further workup
• Factor V leiden mutation • Prothombin gene mutation• MTHFR gene mutation
• Protein S functional assay ( Total, free ) • Protein C functional assay
![Page 28: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/28.jpg)
Practical points
• In acute phase levels of protein C ,S etc may not be accurate , so should be repeated again
• Patient should be off anti-coagulants for at least 2-3 weeks (Protein C and S are reduced due to heparin, oral anti coagulants )
![Page 29: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/29.jpg)
Iron deficiency Anemia
• Headache• fatigue• Restless leg syndrome• Ischemic Stroke ( due to Thrombocytosis)
![Page 30: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/30.jpg)
Polycythemia
• Arterial ischemic stroke• Hyper viscosity
syndrome:headache,dizziness,tinnitus,visual blurring,cognitive changes, paresthesias
• Pseudotumur cerebri
• Chorea• Erythromelalgia : painful, hot, red extremities ( small
fiber autonomic dysfunction)
![Page 31: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/31.jpg)
Sickle cell anaemia
• Ischemic stroke• Hemorrhagic stroke• Seizure • Sensrineural Deafness• Retinopathy, blindness • Moya moya syndrome• Pneumococcal meningitis
![Page 32: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/32.jpg)
Thalassemia
• Transient dizziness• Visual blurring• Headache • seizure• Occasional ischemic/hemorrahgic stroke • Motor neuropathy• Spinal cord compression ( Extramedullary
hematopoiesis)
![Page 33: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/33.jpg)
Hemophillia
• ICH often without trauma • Subdural,epidural,intrcerebal,intra spinal • Hematomas can compress peripheral nerves • 3% risk, but mortality is 35% ( over 10 yrs) • Treatment with factor concentrate
![Page 34: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/34.jpg)
Leukemia
• ALL : 5-10% has CNS involvement at diagnosis( leptomeningeal involvement)
Headache, cranial neuropathy, meningismus, cognitive changes, gait, Sphincter disturbances
• AML : less CNS involvement ; chloroma ( granulocytic sarcoma)
![Page 35: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/35.jpg)
Leptomeningeal metastasis
• Common: Leukemia,lymphoma,breast,lung,melanoma
• Symptoms: Headache, N/V,meningismus,cognitive changes, incontinence , cranial neuropathy, radiculopathy
• Diagnosis:MR brain and spine with contrastCSF : 10 ml ( large volume) ,repeated tests , prompt
examination,cytology, flow cytometry
![Page 36: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/36.jpg)
![Page 37: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/37.jpg)
lymphoma
• Hodgkins lymphoma : rare , epidural spinal compression
• NHL : CNS involvement common ( meningeal lymphamatosis)
• Primary CNS Lymphoma ( HIV, transplant patients) : Corpus Callosum , deep Periventricular white matter , frontal lobe
![Page 38: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/38.jpg)
Plasmacell dyscrasias• MGUS : peripheral neuropathy • Multiple myeloma: spinal cord compression, radiculopathy • POEMS syndrome: CIDP like neuropathy• Waldenstrom macroglobulinemia : sensory-motor peripheral
neuropathy , Hyperviscocity syndrome
• Amylodosis: small fiber autonomic neuropathy, Carpal tunnel syndrome
• Hyper viscosity syndrome, hypercalcemia,renal failure ,infection
![Page 39: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/39.jpg)
Practical point
• Any patient with undiagnosed ployneuropathy should be investigated with
• ESR• Sr Proteins• Sr Protein Electrophoresis (SPEP) , IEP ( Immuno-ElectroPhoresis) • Urine for BJP
![Page 40: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/40.jpg)
Hyperviscocity Syndromes
• Blood is much thicker • Normal viscocity : 1.4 to 1.8 cp (centi-poise) units • HVS occurs at > 4-5 units • Increses cells , immunoglobulins ( Polycythemia, leukemia,MM,WM)• S&S: Visual , Neurological , mucosal bleeding• It is an emergency • Rx: Hydration, removal by phlebotomy or apheresis ,
treatment of underlying disorder
![Page 41: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/41.jpg)
Thrombotic Thrombocytopenic Purpura
Pentads of TTP 1. Fever2. Hemolytic anemia (microangiopathic)3. Thrombocytopenia ( purpura)4. Renal dysfunction5. Neurological (CNS) symptoms -fluctuating( TIA, seizure,altered behavior, coma)
![Page 42: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/42.jpg)
• Treatment: Plex, IVIg, splenectomy, corticosteroids
![Page 43: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/43.jpg)
APLA syndrome :
• Migraine• Amaurosis Fugax ,Ischemic Optic Neuropathy (ION)• Arterial or venous ischemic stroke• MS like lesions
• Thrombocytopenia, false positive VDRL, prolonged aPTT, Bad obstetric history
![Page 44: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/44.jpg)
Thrombocytopenia & Neurological disorders ( stroke,seizure,TIAs,encephalopathy)
Mental check list:1) TTP2) LUPUS (SLE)3) APLA Syndrome/ Sneddon syndrome4) AIDS / HIV5) Heparin induced thrombocytopenia(HIT) 6) Valproate induced thrombocytopenia 7) Wilson disease ( Hemato/neuro)
![Page 45: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/45.jpg)
Idiopathic hypereosinophillia Syndrome (IHES)
• > 1500 AEC ( absolute eosinophil count)• Parasitic infection, drugs, allergies, Collagen vascular
disease ( esp Chrug Strauss disease), few leukemias• >1500, > 6 M , No other cause, organ damage
Idiopathic HES • Organs : heart, skin, lung, GI, nervous system • Neurological manifestations: encephalopathy,infarcts,
neuropathies ( MMN,sensory), • Treatment: Aspirin, Steroids, Hydroxyurea
![Page 46: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/46.jpg)
Arterial ischemic stroke and homocysteine
• Hyperhomocysteinemia Recommendations:
• 1 )Routine screening for hyperhomocysteinemia among patients with a recent ischemic stroke or TIA is not indicated
• 2)In adults with a recent ischemic stroke or TIA who are known to have mild to moderate hyperhomocysteinemia, supplementation with folate, vitamin B6and vitamin B12safely reduces levels of homocysteine ,but has not been
shown to prevent stroke .
![Page 47: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/47.jpg)
Nutritional deficiencies
• Vitamin B12 deficiency : SACD ( Subacute Combined degeneration)
![Page 48: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/48.jpg)
Rare disorders
• Histiocytosis X• PNH ( Paroxysmal Nocturnal Hemoglobinuria) • Porphyrias• DIC• GVHD• Transplant complications
![Page 49: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/49.jpg)
Drugs used in Hematological disorders with neurological side effects
• 5 FU : Toxic leukoencephalopathy• Cisplatinum: Sensory
neuronopathy/Ganglionopathy• Cytosine arabinoside : Cerebellar syndrome • L Asparginase: venous sinus thrombosis• Intrathecal Methotraxate neurotoxicity
![Page 50: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/50.jpg)
HEMOGRAM REPORTTEST RESULT UNIT NORMAL RANGE
HEMOGLOBIN : 11.0 gms/100ml [13.0-17; F: 12.0-15.0]
TOTAL W.B.C. : 7,900 per cu.mm [4,000-11000]
PLATELET COUNT : 2,53,000 per c.mm [1,50,000-4,00,000]
DIFFERENTIAL COUNT Neutrophils : 73 % [40-70 %]
Lymphocytes : 25 % [20-40 %]
Eosinophils : 01 % [00-04 %]
Monocytes : 01 % [01-06 %]
Basophils : 00 % [00-0.5 %]
BLOOD INDICESRBC : 4.03 Million/cmm [M 4.5-5: F 3.8-4.8]
PCV : 34.0 % [M 41-51; F 36-45%]
MCV : 84.3 % [ 80-95 %]
MCH : 27.2 cu.micron [27-32 cu.micron]
MCHC : 32.3 % [32-36%]
ERYTHROCYTE SEDIMENTATION RATE1ST Hour E.S.R. : 06 mmHg Men Women
17-50 yr <10 <12
51-60 yr <12 <19
61-70 yr <14 <20
>70 yr <30 <35
ALWAYS EXAMINE HEMOGRAM METICUOUSLY
![Page 51: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/51.jpg)
Take home message • Head is attached to the body !!
• V : vascular• I : Infective• T : Traumatic , Toxic• A : Allergic , anaphylactic • I : Inflammatory ( Demyelinating)• N: Nutritional , neoplastic• S : Systemic
![Page 52: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/52.jpg)
• Basic investigation:
Good hemogram (and a communicative pathologist)
![Page 53: Neurological manifestations of Hematological disorders](https://reader035.vdocuments.us/reader035/viewer/2022070520/58f9b1b4760da3da068bc373/html5/thumbnails/53.jpg)
Thank You