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MEDICAL GRANDROUNDS Marion Priscilla B. Aurellado, M.D. May 22, 2008 Objectives To present a case of cerebral toxoplasmosis To discuss an approach to right upper extremity weakness in a young, previously healthy patient with mass lesions in the brain on imaging To present some epidemiologic data on the burden of HIV/AIDS in the Philippines Identifying Data J.E. 27 year old male Single Filipino Roman Catholic From Pangasinan Chief Complaint Near syncopal attack History of Present Illness 3 months Intermittent dizziness Light headedness No meds/consult History of Present Illness 2 weeks RUE weakness Weak hand grip Orthopedic consult done Unrecalled meds given Advised observation Progression of right weakness Follow-up consult done EMG-NCV advised, but not done History of Present Illness 2 days generalized body weakness Admission Near syncopal attack Clinic consult done Hypotensive at 80/60 Advised admission Review of Systems (+) weight loss ~ 30 lbs in 4 months (+) undocumented intermittent fever & chills since 4 months (+) anorexia (+) hair loss (-) headache (-) loss of consciousness (-) cough or colds (-) chest pain (-) dyspnea (-) palpitations (-) abdominal pain (-) nausea or vomiting (-) LBM/constipation (-) melena (-) hematochezia (-) dysuria (-) hematuria Past Medical History No asthma No DM No history of hepatitis No previous hospitalizations No history of blood transfusions No known food or drug allergies Family History (+) DM Social History Non-smoker Occasional alcoholic beverage drinker No illicit drug use Physical Examination General Survey: Conscious, coherent, not in respiratory distress Vital Signs: BP lying: 100/60 BP sitting: 100/60 BP standing: 80/50 CR 88 RR 18 afebrile HEENT: Pink palpebral conjunctivae, anicteric sclerae, (-) tonsillopharyngeal congestion, (-) cervical lymphadenopathies Physical Examination Chest & Lungs: Symmetric chest expansion, clear breath sounds CVS: Adynamic precordium, normal rate, regular rhythm, no murmurs Abdomen: Flat abdomen, normoactive bowel sounds, no tenderness, no organomegaly Physical Examination Extremities: Full and equal pulses, no edema, (+) purplish skin rash all over, (+) atrophy of dorsal interossei muscles of right hand (claw hand appearance), (+) subcutaneous nodules in all extremities Neurologic Examination Mental Status Exam: awake, oriented to 3 spheres no memory lapses, good attention intact repetition, recall 3/3 no aphasia, no R-L disorientation Neurologic Examination Cranial Nerves: CN I - intact CN II – pupils 3-4 mm EBRTL, visual fields intact CN III, IV, VI – primary gaze midline, full EOMs CN V – intact V1-V3 CN VII – no facial asymmetry CN VIII - intact CN IX, X – intact gag CN XI – good SCM tone CN XII – tongue midline Neurologic Examination Sensory: Intact to all modalities Motor: 5/5 on both lower extremities and LUE RUE: 5-/5 shoulder abduction 4/5 shoulder adduction 4/5 Shoulder extension 5-/5 shoulder flexion 5-/5 elbow flexion 4/5 elbow extension Neurologic Examination Cerebellum: No dysdiadochoinesia, no dysmetria, able to walk in tandem, walk on heels and toes Deep Tendon Reflexes: +2 left; +3 right upper extremity, +2 right lower extremity Pathologic Reflexes: no Babinski Meninges: no nuchal rigidity Salient Features 27 year old male Previously healthy Right upper extremity weakness, dizziness Significant weight loss & anorexia Intermittent fever Generalized skin rash Atrophy of dorsal interossei muscles of right hand (claw hand appearance) Subcutaneous nodules in all extremities Where is the Lesion? Focal peripheral nerve involvement What is the Nature of the Lesion? Metabolic Inflammatory Trauma Thomas PK, Ochoa J. Symptomatology and differential diagnosis of peripheral neuropathy. In: Dyck PJ, Thomas PK, eds. Peripheral neuropathy. Philadelphia: Saunders, 1993:749-74. Admitting Impression Connective Tissue Disease Course in the Wards 12 L ECG Stat 5 IV Fluids started ESR and ANA EMG-NCV st 1 Hospital Day BP stable 100-110/60-70 No dizziness (+) R arm weakness ESR 120 Impression: Connective tissue disease nd 2 Hospital Day Prednisone started EMG NCV R arm - NORMAL ANA negative Impression: Connective tissue disease ruled out nd 2 Repeat CBC Hospital Day Anemia & eosinophilia Fecalysis Dermatology referral: Skin biopsy Impression: Parasitic infection MRI & MRA with Gadolinium Salient Features Subcutaneous nodules in all extremities Anemia, eosinophilia Multiple ring enhancing lesions on cranial MRI Impression: T/C Neurocysticercosis R/O CNS Malignancy Multiple Ring Enhancing Lesions on MRI Neoplastic Primary Infectious Metastatic Multiple Ring Enhancing Lesions on MRI Neoplastic Infectious Bacterial Tuberculoma Abscess Cryptococcus Neurocysticercosis Toxoplasmosis Primary CNS Lymphoma Present with one of 3 syndromes Subacute progression of focal neurologic deficit Seizure Nonfocal neurologic deficit: Headache Fever, malaise, weight loss, anorexia suggest metastatic more than primary Uniformly enhancing mass lesion in immunocompetent Ring enhancing in the immunocompromised Metastatic Brain Tumors Most commonly originates from: Lung CA Breast CA GI malignancy Melanoma Bacterial Brain Abscess Cause: Streptococcus (40%), Anaerobes, Staphylococcus (10%) Associated with otitis, mastoiditis, dental infections or head trauma Headache is the most common symptom in >75% of cases Classic triad of headache, fever, and focal neurologic deficit Multiple hematogenous poorly encapsulated Tuberculoma Uncommon manifestation of CNS tuberculosis Cause: Mycobacterium tuberculosis Transmission: Hematogenous spread from a primary pulmonary or postprimary pulmonary disease Seizures or focal neurologic deficits Diagnosis: AFB on CSF Neurocysticercosis Cause: Taenia solium Transmission: Ingestion of undercooked pork Cysticerci found anywhere in the body but are commonly in: Brain CSF Skeletal muscle Subcutaneous tissue Eye Neurocysticercosis Often presents with seizures and signs of increased intracranial pressure Diagnosis: Fecalysis Neuroimaging Evidence of cysticercosis outside the CNS Cryptococcosis Cause: Cryptococcus neoformans Transmission: inhalation of yeast from the environment (bird droppings) Risk factor: CD4 < 100 Presents with headache, fever, cranial nerve paresis, and meningeal irritation Diagnosis: India ink stain, CALAS Toxoplasmosis Cause: Toxoplasma gondii Transmission: Ingestion of faecally contaminated material, Ingestion of undercooked meat Risk factor: CD4 < 100 Asymptomatic in immunocompetent people Toxoplasmosis In immunocompromised, mainly involve the CNS Altered mental status (75%) Focal neurologic deficits (60%) Headaches (56%) Seizures (33%) Diagnosis: Serology: IgG and IgM rd 3 Hospital Day Mannitol started Lumbar puncture done Opening pressure 120 cmH2O Clear WBC 2 Lymphocytes 2 RBC 0 Sugar 64 (nv 40-75); Protein 47.4 (15-45) No organisms or pus cells Negative for AFB, India Ink, KOH, CALAS Dexamethasone started th 4 Hospital Day X-ray of the left femur – NORMAL Infectious Diseases referral History of unprotected sex with multiple sexual partners and bisexual contacts HIV screening Whole abdomen UTZ – NORMAL Multiple Ring Enhancing Lesions on MRI Neoplastic Primary Infectious Metastatic Multiple Ring Enhancing Lesions on MRI Neoplastic Infectious Bacterial Tuberculoma Abscess Cryptococcus Neurocysticercosis Toxoplasmosis th 8 Hospital Day CD4 count Serum CALAS Toxoplasma IgG Toxoplasma IgM th 9 Hospital Day Discharged, awaiting final report: Serum CALAS Toxoplasma IgG Toxoplasma IgM CD4 titers and HIV test Patient Outcome HIV (+); CD4 = 53 Toxoplasma IgG 3.8 (nv <2) Toxoplasma IgM 0.34 (nv <0.5) Serum CALAS NEGATIVE Clinical Correlation Toxoplasmosis Patient JE Nonfocal to focal neurologic deficits Meningeal involvement uncommon CSF often unremarkable, may have modest increase in cell count & protein but normal glucose CD4 < 100 Motor deficit (RUE) Absence of meningismus Sugar 64 (nv 40-75); Protein 47.4 (15-45) CD4: 53 Clinical Correlation Toxoplasmosis Patient JE (+) IgG titers detected as early as 2-3 weeks after infection Multiple discrete high signal foci, heterogenous w/ wellcircumscribed margins, and hyperintense on post contrast MRI Toxoplasma IgG 3.8 (<2) Toxoplasma IgM normal Multiple ring enhancing lesions with vasogenic edema in both cerebral hemispheres at the corticomedullary margin Final Diagnosis Cerebral Toxoplasmosis HIV infection Atopic Dermatitis Management Toxoplasmosis is rapidly fatal if untreated Treatment of choice: Pyrimethamine plus folinic acid plus sulfadiazine Pyrimethamine plus folinic acid plus clindamycin Danneman et al. Ann Intern Med 1992; 116:33-43. 6 weeks therapy at least, or until 3 weeks after complete scan resolution Corticosteroids for raised intracranial pressure Cohn et al. Am J Med 1989; 86: 521-7 Management Oral co-trimoxazole is effective in doses of 2 tablets 4 times daily for 1 month followed by 2 tablets twice daily as secondary prophylaxis for life Lifetime prophylactic therapy for toxoplasmosis would only apply if patients are not receiving antiretroviral therapy with the CD4 count being under 200 cells/μl P Francis, January 2004, Vol. 94, No. 1 S Afr Med J HIV Ab Seropositives by Year HIV/AIDS Registry, January 1984-July 2007 (N=2,916 HIV Ab Seropositives by Gender and Age Group HIV/AIDS Registry, January 1984-July 2007 (N=2,916) Reported Modes of Transmission HIV/AIDS Registry, January 1984-July 2007 (N=2,916) Mode Jan 84 -July 07 July 07 Heterosexual Contact 1781 10 Homosexual Contact 567 9 Bisexual Contact 200 9 Blood/Blood product 19 0 IV drug use 7 0 Reported Modes of Transmission HIV/AIDS Registry, January 1984-July 2007 (N=2,916) Needle prick injuries 3 0 Perinatal 44 0 No exposure reported 295 3 TOTAL 2916 31 Patient Outcome Readmitted after 2 weeks for seizure Started on Co-trimoxazole and ARTs Discharged against medical advice Went back to Pangasinan Lost to follow-up AMD notified by company physician that the patient expired Thank you!!!