Neurological manifestations of Hematological disorders
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Transcript of Neurological manifestations of Hematological disorders
Neurological Manifestations of Hematological Disorders
DR Bipin Bhimani DM ( Neurology)(NIMHANS)
Well Care Hospital Rajkot
4 Situations
• Scenario 1:
• Known case of hematological disorder leading to neurological problem
• Eg :k/c/o sickle Cell Anemia gets ischemic stroke
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.
Scenario 3
• A multisystem disorder affecting both hemato and neuro system
• Eg:A lady with psychosis and thrombocytopenia , turn outs to have SLE
Scenario 4
• Neurological side effect of a drug used for hematological disorder
• Eg: Vincristine induced polyneuropathy
• Eg: 5 F-U causing Toxic leukoencephalopathy
Case 1
• Boy with limping gait
• Orthopedic opinion: Normal xrays, CRP, ASO, RA
• Neuro opinion: Hemogram
• Leukemia with blast crisis ( leading to joint pain )
Case 2:
• Man with headache , early papilloedema • Normal CT and limited MR brain
• High MCV
• Cerebral Venous sinus thrombosis on MR venogram ( due to high Homocysteine /Low B12 )
Case 3:
• Patient with fluctuating symptoms ? Seizures, TIAs, and behavioral changes
• Near normal MR brain
• Blood Ix: Thrombocytopenia
• TTP ( Thrombotic thrombocytopenic Purpura)
Case 4:
• Girl with bilateral watershed infarcts
• ( No hypotension, normal carotid doppler, MRAngio brain, 2 D Echo )
• Idiopathic hypereosinophilia syndrome with neurotoxicity
Case 5:
• Thallasemic girl with paraplegia
• Extramedullary hematopoesis in spinal canal, compressing spinal cord
Hypercoaguble disorders and ischemic stroke
• Pump ( heart)• Pipe ( artery) • Passage ( blood)
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
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
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
Thrombophilia work up ( Basic)
• Hemogram• PT, aPTT• Homocystiene• ANA, VDRL• LA, ACLA • APLA • Anti-Thrombin III level• Pro Ce globe
Further workup
• Factor V leiden mutation • Prothombin gene mutation• MTHFR gene mutation
• Protein S functional assay ( Total, free ) • Protein C functional assay
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 )
Iron deficiency Anemia
• Headache• fatigue• Restless leg syndrome• Ischemic Stroke ( due to Thrombocytosis)
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)
Sickle cell anaemia
• Ischemic stroke• Hemorrhagic stroke• Seizure • Sensrineural Deafness• Retinopathy, blindness • Moya moya syndrome• Pneumococcal meningitis
Thalassemia
• Transient dizziness• Visual blurring• Headache • seizure• Occasional ischemic/hemorrahgic stroke • Motor neuropathy• Spinal cord compression ( Extramedullary
hematopoiesis)
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
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)
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
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
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
Practical point
• Any patient with undiagnosed ployneuropathy should be investigated with
• ESR• Sr Proteins• Sr Protein Electrophoresis (SPEP) , IEP ( Immuno-ElectroPhoresis) • Urine for BJP
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
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)
• Treatment: Plex, IVIg, splenectomy, corticosteroids
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
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)
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
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 .
Nutritional deficiencies
• Vitamin B12 deficiency : SACD ( Subacute Combined degeneration)
Rare disorders
• Histiocytosis X• PNH ( Paroxysmal Nocturnal Hemoglobinuria) • Porphyrias• DIC• GVHD• Transplant complications
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
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
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
• Basic investigation:
Good hemogram (and a communicative pathologist)
Thank You